KNSTRN

Chr 15Digenic recessive

kinetochore localized astrin (SPAG5) binding protein

Also known as: C15orf23, HSD11, ROCHIS, SKAP, TRAF4AF1

NCBI Gene: 90417 ENSG00000128944 UniProt: Q9Y448 OMIM: 614718

Enables microtubule plus-end binding activity and protein homodimerization activity. Involved in several processes, including cellular response to epidermal growth factor stimulus; mitotic sister chromatid segregation; and regulation of attachment of spindle microtubules to kinetochore. Located in kinetochore; microtubule cytoskeleton; and ruffle. Implicated in actinic keratosis and skin squamous cell carcinoma. [provided by Alliance of Genome Resources, Jun 2026]

OMIM Research

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

?Roifman-Chitayat syndrome, digenicMIM #613328

Digenic recessive

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.98

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.98LOEUF

pLI 0.000

Z-score 1.63

OE 0.61 (0.39–0.98)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.46Z-score

OE missense 1.10 (0.97–1.24)

184 obs / 167.2 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.61 (0.39–0.98)

0≤0.351.4

Missense OE?1.10 (0.97–1.24)

0≤0.61.4

Synonymous OE?1.17

0≤1.21.6

LoF obs/exp: 12 / 19.8Missense obs/exp: 184 / 167.2Syn Z: -1.10

Background carrier burden — how many people carry a rare variant somewhere in KNSTRN?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 120

499 rare PASS variants

Rare truncating (LoF)

1 in 790

107 rare PASS variants

Rare synonymous (reference)

1 in 250

180 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for KNSTRN. 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 180	1 in 680
South Asian	~43k	1 in 100	1 in 630
Remaining (unassigned)	~30k	1 in 89	1 in 1,100
European (Finnish)	~27k	1 in 190	1 in 1,600
Admixed American	~22k	1 in 84	1 in 1,000
African / African American	~21k	1 in 100	1 in 1,200
East Asian	~20k	1 in 97	1 in 960
Ashkenazi Jewish	~13k	1 in 440	≈ 1 in 6,500
Middle Eastern	~2,884	1 in 93	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 9 coding exons well covered in gnomAD exomes and genomes.? see exons ↓