KRTAP10-9

Chr 21

keratin associated protein 10-9

Also known as: KAP10.9, KAP18.9, KRTAP18-9

NCBI Gene: 386676 ENSG00000221837 UniProt: P60411

The KRTAP10-9 protein is a hair keratin-associated protein that forms extensive disulfide cross-links with hair keratins to create the rigid matrix essential for normal hair shaft formation. Currently, no human diseases have been definitively associated with mutations in this gene. This gene shows very low constraint against loss-of-function variants, suggesting that complete loss of this protein may be well-tolerated.

Summary from RefSeq, UniProt

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Active trials

Pubs (1 yr)

P/LP submissions

P/LP missense

1.78

LOEUF

Multiple*

Mechanism· predicted

Clinical Summary— KRTAP10-9

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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

88 unique Pathogenic / Likely Pathogenic· 107 VUS of 207 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint

1.78LOEUF

pLI 0.000

Z-score -0.10

OE 1.04 (0.58–1.78)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint

-1.77Z-score

OE missense 1.39 (1.25–1.55)

227 obs / 163.3 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios

LoF OE1.04 (0.58–1.78)

0≤0.351.4

Missense OE1.39 (1.25–1.55)

0≤0.61.4

Synonymous OE1.80

0≤1.21.6

LoF obs/exp: 7 / 6.7Missense obs/exp: 227 / 163.3Syn Z: -5.37

0.90top 5%

GOF

0.77top 25%

LOF

0.3551th %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.