TYRO3

Chr 15

TYRO3 protein tyrosine kinase

Also known as: BYK, Dtk, Etk-2, RSE, Rek, Sky, Tif

NCBI Gene: 7301 ENSG00000092445 UniProt: Q06418 OMIM: 600341

The gene is part of a 3-member transmembrane receptor kinase receptor family with a processed pseudogene distal on chromosome 15. The encoded protein is activated by the products of the growth arrest-specific gene 6 and protein S genes and is involved in controlling cell survival and proliferation, spermatogenesis, immunoregulation and phagocytosis. The encoded protein has also been identified as a cell entry factor for Ebola and Marburg viruses. [provided by RefSeq, May 2010]

OMIM Research

OMIM ResearchGenerating clinical summary…

Active trials

107

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.74

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.74LOEUF

pLI 0.000

Z-score 2.93

OE 0.52 (0.37–0.74)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.57Z-score

OE missense 0.80 (0.74–0.87)

413 obs / 513.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.52 (0.37–0.74)

0≤0.351.4

Missense OE?0.80 (0.74–0.87)

0≤0.61.4

Synonymous OE?0.99

0≤1.21.6

LoF obs/exp: 22 / 42.7Missense obs/exp: 413 / 513.3Syn Z: 0.06

Background carrier burden — how many people carry a rare variant somewhere in TYRO3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 49

938 rare PASS variants

Rare truncating (LoF)

1 in 860

100 rare PASS variants

Rare synonymous (reference)

1 in 92

414 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TYRO3. 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 50	1 in 730
South Asian	~43k	1 in 42	1 in 470
Remaining (unassigned)	~30k	1 in 44	1 in 470
European (Finnish)	~27k	1 in 190	1 in 1,600
Admixed American	~22k	1 in 49	1 in 330
African / African American	~21k	1 in 75	1 in 1,800
East Asian	~20k	1 in 66	1 in 650
Ashkenazi Jewish	~13k	1 in 300	1 in 1,400
Middle Eastern	~2,884	1 in 44	≈ 1 in 1,200

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): 18 of 19 coding exons well covered in gnomAD exomes; exon 1 poorly covered. Genomes: 18 of 19 (exon 1 below).? see exons ↓