NKX6-3

Chr 8

NK6 homeobox 3

Also known as: NKX6.3

NCBI Gene: 157848 ENSG00000165066 UniProt: A6NJ46 OMIM: 610772

The NKX family of homeodomain proteins controls numerous developmental processes. Members of the NKX6 subfamily, including NKX6-3, are involved in development of the central nervous system (CNS), gastrointestinal tract, and pancreas (Alanentalo et al., 2006 [PubMed 16326147]).[supplied by OMIM, Mar 2008]

OMIM Research

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.57

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.57LOEUF

pLI 0.016

Z-score 0.72

OE 0.64 (0.29–1.57)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.11Z-score

OE missense 1.04 (0.86–1.26)

75 obs / 72.3 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.64 (0.29–1.57)

0≤0.351.4

Missense OE?1.04 (0.86–1.26)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 3 / 4.7Missense obs/exp: 75 / 72.3Syn Z: -0.10

Background carrier burden — how many people carry a rare variant somewhere in NKX6-3?

gnomAD v4 · ~730k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

461 rare PASS variants

Rare truncating (LoF)

1 in 2,000

83 rare PASS variants

Rare synonymous (reference)

1 in 230

219 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for NKX6-3. 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 210	1 in 2,400
South Asian	~43k	1 in 89	1 in 910
Remaining (unassigned)	~30k	1 in 110	1 in 2,300
European (Finnish)	~26k	1 in 150	1 in 3,100
Admixed American	~22k	1 in 97	1 in 1,200
African / African American	~21k	1 in 190	1 in 1,300
East Asian	~20k	1 in 150	≈ 1 in 9,400
Ashkenazi Jewish	~13k	1 in 1,100	none seen
Middle Eastern	~2,879	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 3 coding exons well covered in gnomAD exomes and genomes.? see exons ↓