CCDC47

Last update 08 May 2025

Basic Info

Synonyms

Calumin, CCDC47, coiled-coil domain containing 47

+ [3]

Introduction

Component of the multi-pass translocon (MPT) complex that mediates insertion of multi-pass membrane proteins into the lipid bilayer of membranes (PubMed:32814900, PubMed:32820719, PubMed:36261522). The MPT complex takes over after the SEC61 complex: following membrane insertion of the first few transmembrane segments of proteins by the SEC61 complex, the MPT complex occludes the lateral gate of the SEC61 complex to promote insertion of subsequent transmembrane regions (PubMed:36261522). Within the MPT complex, the PAT subcomplex sequesters any highly polar regions in the transmembrane domains away from the non-polar membrane environment until they can be buried in the interior of the fully assembled protein (By similarity). Within the PAT subcomplex, CCDC47 occludes the lateral gate of the SEC61 complex (By similarity). Involved in the regulation of calcium ion homeostasis in the ER (PubMed:30401460). Required for proper protein degradation via the ERAD (ER-associated degradation) pathway (PubMed:25009997). Has an essential role in the maintenance of ER organization during embryogenesis (By similarity).

100 Clinical Results associated with CCDC47

100 Translational Medicine associated with CCDC47

0 Patents (Medical) associated with CCDC47

Literatures (Medical) associated with CCDC47

01 Jan 2025·American Journal of Medical Genetics Part A

CCDC47 gene and trichohepatoneurodevelopmental syndrome: Report of the fifth and sixth cases from Saudi Arabia

Article

Author: Anikar, Swathi ; Zonic, Emir ; Davies, William ; Alsubeeh, Najlaa A. ; Almuqbil, Mohammed A. ; Bertoli‐Avella, Aida ; Eyaid, Wafaa M.

AbstractTrichohepatoneurodevelopmental syndrome (THNS) is an ultra‐rare and complex disorder affecting multiple organ systems. It is characterized by liver dysfunction, hypotonia, global developmental delay, coarse hair, and dysmorphic features. We describe two cases of THNS of Saudi origin, the fifth and sixth cases in the medical literature. Both cases presented with multiple dysmorphic features, generalized hypotonia, global developmental delay, and high liver enzyme level. Exome sequencing of Case 1 identified a pathogenic homozygous variant within the CCDC47: NM_020198.2:c.567_570del, p.(Glu190Profs*7). Genome sequencing of Case 2 identified two likely pathogenic heterozygous variants within the CCDC47: NM_020198.2:c.1327C>T, p.(Arg443*) and NM_020198.2:c.422dup, p.(Leu141Phefs*19). The trans phase of the detected variants has been confirmed by the parental testing. Furthermore, we evaluated the gene–disease association as per ClinGen guidelines and reached a strong level of association after inclusion of the new patients/variants. The findings from these cases will help to delineate the clinical phenotype and the mutational spectrum of this complex disorder.

01 Nov 2024·The American Journal of Human Genetics

Homozygous variants in WDR83OS lead to a neurodevelopmental disorder with hypercholanemia

Article

Author: Posey, Jennifer E. ; Huber, Ilka ; Trimouille, Aurélien ; Busk, Øyvind L. ; Lupski, James R ; Wali, Sami ; Bauer, Peter ; Ghayoor Karimiani, Ehsan ; Mitani, Tadahiro ; Shervin Badv, Reza ; Holla, Øystein L ; Tveten, Kristian ; Houlden, Henry ; Beiraghi Toosi, Mehran ; Zifarelli, Giovanni ; Barish, Scott ; Marafi, Dana ; Maroofian, Reza ; Alkuraya, Fowzan S. ; Fatih, Jawid M ; Alswaid, Abdulrahman ; Petree, Cassidy ; Lupski, James R. ; Al Safar, Ayat ; Gezdirici, Alper ; Huang, Kevin ; Biderman Waberski, Marta ; Busk, Øyvind L ; Holla, Øystein L. ; Varshney, Gaurav K ; Varshney, Gaurav K. ; Akhondian, Javad ; Lin, Sheng-Jia ; Alkuraya, Fowzan S ; von der Lippe, Charlotte ; Eghbal, Fatemeh ; Najarzadeh Torbati, Paria ; Calame, Daniel G ; Alhebby, Hamoud ; Fatih, Jawid M. ; Calame, Daniel G. ; Pehlivan, Davut ; Posey, Jennifer E

WD repeat domain 83 opposite strand (WDR83OS) encodes the 106-aa (amino acid) protein Asterix, which heterodimerizes with CCDC47 to form the PAT (protein associated with ER translocon) complex. This complex functions as a chaperone for large proteins containing transmembrane domains to ensure proper folding. Until recently, little was known about the role of WDR83OS or CCDC47 in human disease traits. However, biallelic variants in CCDC47 were identified in four unrelated families with trichohepatoneurodevelopmental syndrome, characterized by a neurodevelopmental disorder (NDD) with liver dysfunction. Three affected siblings in an additional family share a homozygous truncating WDR83OS variant and a phenotype of NDD, dysmorphic features, and liver dysfunction. Using family-based rare variant analyses of exome sequencing (ES) data and case matching through GeneMatcher, we describe the clinical phenotypes of 11 additional individuals in eight unrelated families (nine unrelated families, 14 individuals in total) with biallelic putative truncating variants in WDR83OS. Consistent clinical features include NDD (14/14), facial dysmorphism (13/14), intractable itching (9/14), and elevated bile acids (5/6). Whereas bile acids were significantly elevated in 5/6 of individuals tested, bilirubin was normal and liver enzymes were normal to mildly elevated in all 14 individuals. In three of six individuals for whom longitudinal data were available, we observed a progressive reduction in relative head circumference. A zebrafish model lacking Wdr83os function further supports its role in the nervous system, craniofacial development, and lipid absorption. Taken together, our data support a disease-gene association between biallelic loss-of-function of WDR83OS and a neurological disease trait with hypercholanemia.

01 Mar 2024·Heliyon

Clinical and genetic analysis of trichohepatoneurodevelopmental syndrome caused by a CCDC47 variant

Article

Author: Qin, Zailong ; Yi, Shang ; Zhang, Shujie ; Ling, Yeying ; Luo, Jingsi ; Yang, Qi ; Zhang, Qiang ; Zhou, Xunzhao ; Chen, Qiuli

Trichohepatoneurodevelopmental syndrome is an extremely uncommon autosomal recessive disorder resulting from variants in the CCDC47 gene, which encodes a Ca2⁺-binding endoplasmic reticulum (ER) transmembrane protein. To date, only four patients with CCDC47 deficiency have been reported, all of them with homozygous truncating CCDC47 variants. For this study, a Chinese family was recruited, which included a patient diagnosed with trichohepatoneurodevelopmental syndrome. Whole exome sequencing (WES) identified the proband's novel homozygous CCDC47 variation (NM_020198: c.634C > T(p.Arg212*). The variant was confirmed to be segregating in the proband and her unaffected relatives through Sanger sequencing. The patient described exhibited a clinical phenotype similar to that of patients with the CCDC47 variant. Compared to reported cases with CCDC47 pathogenic variants, our patients showed a novel complication of hearing impairment. In addition, brain abnormalities, small feet, bilateral hip dislocation, hip dysplasia, overlapping toes, pectus excavatum, scoliosis and narrow chest were not observed in our patient. We also examined five different variations and their corresponding phenotypes from five patients, both in current and previous research. Although some clinical manifestations of trichohepatoneurodevelopmental syndrome were highly variable, the most common phenotypes observed in these patients include microcephaly, profound intellectual disability, severe global development delay, pronounced growth restriction, hypotonia, woolly hair, facial dysmorphism, respiratory and visual abnormalities, gastrointestinal abnormalities, liver dysfunction, pruritus, skeletal and limb abnormalities, congenital heart defects and immunodeficiency. The present report is the first of a Chinese infant with homozygous variant in the CCDC47 gene. We expanded the genetic and phenotypic spectrum associated with trichohepatoneurodevelopmental syndrome.

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CCDC47

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