CCDC91

Chr 12

coiled-coil domain containing 91

Also known as: HSD8, p56

NCBI Gene: 55297ENSG00000123106UniProt: Q7Z6B0

The protein regulates membrane traffic through the trans-Golgi network and functions in cooperation with GGA proteins to sort hydrolases to lysosomes. Mutations cause autosomal recessive intellectual disability with seizures and spasticity. This gene is highly constrained against loss-of-function variants, indicating intolerance to protein-disrupting mutations.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
5
Pubs (1 yr)
33
P/LP submissions
0%
P/LP missense
0.81
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— CCDC91
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
33 unique Pathogenic / Likely Pathogenic· 52 VUS of 98 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.81LOEUF
pLI 0.000
Z-score 2.30
OE 0.51 (0.33–0.81)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.43Z-score
OE missense 0.92 (0.81–1.03)
194 obs / 211.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.51 (0.33–0.81)
0≤0.351.4
Missense OE0.92 (0.81–1.03)
0≤0.61.4
Synonymous OE1.13
0≤1.21.6
LoF obs/exp: 13 / 25.5Missense obs/exp: 194 / 211.6Syn Z: -0.88
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedCCDC91-related palmoplantar keratoderma, punctate typeOTHERAD
DN
0.74top 25%
GOF
0.6442th %ile
LOF
0.2678th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

98 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic30
Likely Pathogenic3
VUS52
Likely Benign3
Benign2
30
Pathogenic
3
Likely Pathogenic
52
VUS
3
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
30
0
30
Likely Pathogenic
0
0
3
0
3
VUS
0
51
1
0
52
Likely Benign
0
3
0
0
3
Benign
0
2
0
0
2
Total05634090

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

View in ClinVar →

Protein Context — Lollipop Plot

CCDC91 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
A novel CCDC91 isoform associated with ossification of the posterior longitudinal ligament of the spine works as a non-coding RNA to regulate osteogenic genes.
Nakajima M et al.·Am J Hum Genet
2023Natural history
A mutation in CCDC91, Homo sapiens coiled-coil domain containing 91 protein, cause autosomal-dominant acrokeratoelastoidosis.
Zhu Y et al.·Eur J Hum Genet
2024
A three-gene signature marks the time to locoregional recurrence in luminal-like breast cancer.
Chiodoni C et al.·ESMO Open
2023
Genome-wide association and functional studies identify a role for matrix Gla protein in osteoarthritis of the hand.
den Hollander W et al.·Ann Rheum Dis
2017Functional
Interstitial 12p Deletion Syndrome: Revised Minimal Critical Region and Review of the Literature.
Privitera F et al.·Genes (Basel)
2026Review
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients