COX7B

Chr XXLD

cytochrome c oxidase subunit 7B

Also known as: APLCC, LSDMCA2

NCBI Gene: 1349ENSG00000131174UniProt: P24311

Cytochrome c oxidase (COX), the terminal component of the mitochondrial respiratory chain, catalyzes the electron transfer from reduced cytochrome c to oxygen. This component is a heteromeric complex consisting of 3 catalytic subunits encoded by mitochondrial genes and multiple structural subunits encoded by nuclear genes. The mitochondrially-encoded subunits function in electron transfer, and the nuclear-encoded subunits may function in the regulation and assembly of the complex. This nuclear gene encodes subunit VIIb, which is highly similar to bovine COX VIIb protein and is found in all tissues. This gene may have several pseudogenes on chromosomes 1, 2, 20 and 22. [provided by RefSeq, Jun 2011]

Primary Disease Associations & Inheritance

Linear skin defects with multiple congenital anomalies 2MIM #300887
XLD
0
Active trials
50
Pathogenic / LP
102
ClinVar variants
9
Pubs (1 yr)
0.4
Missense Z
0.81
LOEUF
Clinical Summary— COX7B
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.67) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
50 Pathogenic / Likely Pathogenic· 29 VUS of 102 total submissions
📖
GeneReview available — COX7B
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.81LOEUF
pLI 0.675
Z-score 1.77
OE 0.00 (0.00–0.81)
Moderately constrained

Typical tolerance to LoF variation

Missense Constraint
0.42Z-score
OE missense 0.79 (0.57–1.10)
25 obs / 31.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.00–0.81)
0≤0.351.4
Missense OE0.79 (0.57–1.10)
0≤0.61.4
Synonymous OE1.30
0≤1.21.6
LoF obs/exp: 0 / 3.7Missense obs/exp: 25 / 31.7Syn Z: -0.76
DN
DN
0.6746th %ile
GOF
0.5660th %ile
LOF
0.4136th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction 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

102 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic48
Likely Pathogenic2
VUS29
Likely Benign18
Benign2
Conflicting3
48
Pathogenic
2
Likely Pathogenic
29
VUS
18
Likely Benign
2
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
0
46
0
48
Likely Pathogenic
0
0
2
0
2
VUS
0
10
19
0
29
Likely Benign
0
2
11
5
18
Benign
0
0
2
0
2
Conflicting
—3
Total212805102

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

View in ClinVar →

COX7B · protein map & ClinVar variants

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

Gene2Phenotype Curations

COX7B-related microphthalmia with linear skin lesions

definitive
Monoallelic X HeterozygousLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 4 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
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