KRTAP5-9

Chr 11

keratin associated protein 5-9

Also known as: KRN1, KRTAP5-1, KRTAP5.9

NCBI Gene: 3846 ENSG00000254997 UniProt: Q6L8H2 OMIM: 148021

This protein is a keratin-associated protein that forms disulfide cross-links with hair keratins to create the rigid matrix of the hair shaft. Mutations in KRTAP5-9 cause autosomal dominant woolly hair, a condition characterized by tightly curled, fine hair texture present from birth. The gene shows low constraint to loss-of-function variants, suggesting tolerance to complete protein loss.

OMIM ResearchSummary from RefSeq, UniProt

Enables identical protein binding activity. Predicted to be involved in epidermis development. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.93

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.93LOEUF

pLI 0.015

Z-score -0.72

OE 1.73 (0.49–1.93)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.13Z-score

OE missense 0.96 (0.80–1.16)

82 obs / 85.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.73 (0.49–1.93)

0≤0.351.4

Missense OE?0.96 (0.80–1.16)

0≤0.61.4

Synonymous OE?0.77

0≤1.21.6

LoF obs/exp: 2 / 1.2Missense obs/exp: 82 / 85.3Syn Z: 1.10

Background carrier burden — how many people carry a rare variant somewhere in KRTAP5-9?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 180

202 rare PASS variants

Rare truncating (LoF)

1 in 6,500

24 rare PASS variants

Rare synonymous (reference)

1 in 950

78 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for KRTAP5-9. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 550	1 in 6,800
South Asian	~43k	1 in 190	≈ 1 in 14,000
Remaining (unassigned)	~30k	1 in 150	1 in 4,300
European (Finnish)	~27k	1 in 1,200	≈ 1 in 13,000
Admixed American	~22k	1 in 280	1 in 3,800
African / African American	~21k	1 in 120	≈ 1 in 21,000
East Asian	~20k	1 in 220	≈ 1 in 6,600
Ashkenazi Jewish	~13k	1 in 400	none seen
Middle Eastern	~2,884	1 in 230	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 1 coding exons well covered in gnomAD exomes and genomes.? see exons ↓