CCDC47

Chr 17AR

coiled-coil domain containing 47

Also known as: GK001, MSTP041, THNS

NCBI Gene: 57003 ENSG00000108588 UniProt: Q96A33 OMIM: 618260

The CCDC47 protein is a component of the multi-pass translocon complex that mediates insertion of multi-pass membrane proteins into the endoplasmic reticulum and regulates ER calcium homeostasis. Autosomal recessive mutations cause trichohepatoneurodevelopmental syndrome, affecting hair, liver, and neurodevelopment. This gene is not highly constrained against loss-of-function variants.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

Enables protein folding chaperone and ribosome binding activity. Involved in ERAD pathway; endoplasmic reticulum calcium ion homeostasis; and multi-pass transmembrane protein insertion into ER membrane. Located in endoplasmic reticulum membrane. Part of multi-pass translocon complex and protein folding chaperone complex. [provided by Alliance of Genome Resources, Jul 2025]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.881 OMIM phenotype

Clinical Summary— CCDC47

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

7 unique Pathogenic / Likely Pathogenic· 50 VUS of 85 total submissions

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GeneReview available — CCDC47

Authoritative clinical overview · Recommended first read

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.88LOEUF

pLI 0.000

Z-score 2.07

OE 0.58 (0.39–0.88)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.04Z-score

OE missense 0.82 (0.73–0.92)

212 obs / 259.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.58 (0.39–0.88)

0≤0.351.4

Missense OE?0.82 (0.73–0.92)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 16 / 27.8Missense obs/exp: 212 / 259.1Syn Z: 0.16

ClinVar Variant Classifications

85 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

Likely Pathogenic6

VUS50

Likely Benign6

Benign5

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	1	0	0	0	1
Likely Pathogenic	6	0	0	0	6
VUS	0	49	1	0	50
Likely Benign	0	0	3	3	6
Benign	0	0	4	1	5
Total	7	49	8	4	68

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

10 pathogenic / likely-pathogenic (of 13) ClinVar copy-number / structural variants overlap CCDC47 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →