KRTAP10-10

Chr 21

keratin associated protein 10-10

Also known as: KAP10.10, KAP18.10, KRTAP18-10, KRTAP18.10

NCBI Gene: 353333 ENSG00000221859 UniProt: P60014

This protein forms part of the keratin-associated protein matrix that cross-links with hair keratins through disulfide bonds to create the rigid structure of hair shafts. KRTAP10-10 mutations have not been definitively associated with human disease in the medical literature. The gene shows low constraint to loss-of-function variation, suggesting it may be tolerant to functional disruption.

Summary from RefSeq, UniProt

Research Assistant →

Active trials

Pubs (1 yr)

P/LP submissions

P/LP missense

1.53

LOEUF

Multiple*

Mechanism· predicted

Clinical Summary— KRTAP10-10

⚡

Population Constraint (gnomAD)

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

📋

ClinVar Variants

88 unique Pathogenic / Likely Pathogenic· 70 VUS of 170 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

1.53LOEUF

pLI 0.005

Z-score 0.69

OE 0.69 (0.34–1.53)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint

-1.23Z-score

OE missense 1.29 (1.15–1.47)

180 obs / 139.1 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios

LoF OE0.69 (0.34–1.53)

0≤0.351.4

Missense OE1.29 (1.15–1.47)

0≤0.61.4

Synonymous OE1.47

0≤1.21.6

LoF obs/exp: 4 / 5.8Missense obs/exp: 180 / 139.1Syn Z: -2.92

0.90top 5%

GOF

0.83top 10%

LOF

0.2679th %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.