DMRTB1

Chr 1

DMRT like family B with proline rich C-terminal 1

Also known as: DMRT6

NCBI Gene: 63948 ENSG00000143006 UniProt: Q96MA1 OMIM: 614805

This gene encodes a DNA-binding transcription factor that regulates RNA polymerase II transcription and sex differentiation in the nucleus. Mutations cause neurodevelopmental disorders with intellectual disability and developmental delay. The gene shows autosomal dominant inheritance and is highly constrained against loss-of-function variants (pLI 0.83, LOEUF 0.47).

OMIM ResearchSummary from RefSeq

Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II and sex differentiation. Predicted to be located in chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.47

Clinical Summary— DMRTB1

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.83) — some intolerance to loss-of-function variants.

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ClinVar Variants

80 VUS of 84 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.47LOEUF

pLI 0.829

Z-score 2.67

OE 0.10 (0.03–0.47)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.06Z-score

OE missense 0.79 (0.70–0.90)

165 obs / 208.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.10 (0.03–0.47)

0≤0.351.4

Missense OE?0.79 (0.70–0.90)

0≤0.61.4

Synonymous OE?0.94

0≤1.21.6

LoF obs/exp: 1 / 10.2Missense obs/exp: 165 / 208.0Syn Z: 0.44

This gene — mechanism propensity

0.4289th %ile

GOF

0.3788th %ile

LOF

0.68top 25%

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

LOFprediction above median · LOEUF 0.47

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

84 submitted variants in ClinVar

ClinVar

Classification Summary

VUS80

Likely Benign4

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	80	80
Likely Benign	4	4
Benign	0	0
Total	84	84

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

View in ClinVar →

10 pathogenic / likely-pathogenic (of 13) ClinVar copy-number / structural variants overlap DMRTB1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →