NKX1-1

Chr 4

NK1 homeobox 1

Also known as: HSPX153, NKX-1.1, SAX2

This gene encodes a transcription factor that belongs to NKX family of homeodomain-containing proteins which are critical regulators of organ development. In mice, the orthologous gene is expressed predominantly in the brainstem, in the vicinity of serotonergic neurons, and is required for the coordinated crosstalk of factors involved in the maintenance of energy homeostasis. Mice with a knockout of the orthologous gene lack subcutaneous fat and intra-abdominal epididymal and mesenteric white adipose tissue two weeks after birth, and die within three weeks after birth. [provided by RefSeq, Jul 2017]

0
Active trials
0
Pubs (1 yr)
143
P/LP submissions
P/LP missense
0.72
LOEUF
LOF
Mechanism· predicted
Clinical SummaryNKX1-1
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.71) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
143 unique Pathogenic / Likely Pathogenic· 14 VUS of 160 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.72LOEUF
pLI 0.715
Z-score 1.88
OE 0.00 (0.000.72)
Moderately constrained

Typical tolerance to LoF variation

Missense Constraint
0.74Z-score
OE missense 0.78 (0.640.95)
67 obs / 86.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.000.72)
00.351.4
Missense OE0.78 (0.640.95)
00.61.4
Synonymous OE1.08
01.21.6
LoF obs/exp: 0 / 4.1Missense obs/exp: 67 / 86.3Syn Z: -0.41
DN
0.3395th %ile
GOF
0.3193th %ile
LOF
0.81top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

160 submitted variants in ClinVar

Classification Summary

Pathogenic137
Likely Pathogenic6
VUS14
Likely Benign1
Benign2
137
Pathogenic
6
Likely Pathogenic
14
VUS
1
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
137
Likely Pathogenic
6
VUS
14
Likely Benign
1
Benign
2
Total160

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

NKX1-1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found