LHX1

Chr 17

LIM homeobox 1

Also known as: LIM-1, LIM1

NCBI Gene: 3975 ENSG00000273706 UniProt: P48742

LHX1 encodes a LIM domain-containing transcription factor that is important for development of the renal and urogenital systems, as well as early mesoderm formation and neurogenesis. Mutations cause Mayer-Rokitansky-Kuster-Hauser syndrome, characterized by anomalies in the female genital tract. The gene shows low constraint against loss-of-function variants (pLI 0.03, LOEUF 0.74), and inheritance pattern information requires further clinical correlation.

GeneReviews ResearchSummary from RefSeq, UniProt

This gene encodes a member of a large protein family which contains the LIM domain, a unique cysteine-rich zinc-binding domain. The encoded protein is a transcription factor important for the development of the renal and urogenital systems. This gene is a candidate for Mayer-Rokitansky-Kuster-Hauser syndrome, a disorder characterized by anomalies in the female genital tract. [provided by RefSeq, Dec 2010]

GeneReviews ResearchGenerating clinical summary…

DNmechanismLOEUF 0.74

Clinical Summary— LHX1

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Population Constraint (gnomAD)

Low constraint (pLI 0.03) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

42 VUS of 56 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — LHX1

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.74LOEUF

pLI 0.029

Z-score 2.27

OE 0.35 (0.18–0.74)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.92Z-score

OE missense 0.64 (0.56–0.74)

146 obs / 227.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.35 (0.18–0.74)

0≤0.351.4

Missense OE?0.64 (0.56–0.74)

0≤0.61.4

Synonymous OE?1.24

0≤1.21.6

LoF obs/exp: 5 / 14.3Missense obs/exp: 146 / 227.6Syn Z: -1.89

This gene — mechanism propensity

0.7133th %ile

GOF

0.5464th %ile

LOF

0.4627th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

ClinVar Variant Classifications

56 submitted variants in ClinVar

ClinVar

Classification Summary

VUS42

Likely Benign9

Benign4

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	42	0	0	42
Likely Benign	1	1	7	9
Benign	1	0	3	4
Total	44	1	10	55

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

138 pathogenic / likely-pathogenic (of 148) ClinVar copy-number / structural variants overlap LHX1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →