KDM1B

Chr 6

lysine demethylase 1B

Also known as: AOF1, C6orf193, LSD2

The KDM1B protein is a histone demethylase that removes methyl groups from lysine-4 of histone H3, acting as a transcriptional corepressor and playing a critical role in DNA methylation of imprinted genes during oogenesis. Loss-of-function mutations in KDM1B cause autosomal recessive intellectual disability with microcephaly through disruption of epigenetic gene regulation. The low pLI score (0.001) and moderate LOEUF score (0.53) indicate this gene is relatively tolerant to heterozygous loss-of-function but pathogenic when both copies are affected.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
2
Pubs (1 yr)
14
P/LP submissions
0%
P/LP missense
0.53
LOEUF
Mechanism
Clinical SummaryKDM1B
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.33) despite low pLI — interpret in context.
📋
ClinVar Variants
14 unique Pathogenic / Likely Pathogenic· 67 VUS of 105 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.53LOEUF
pLI 0.001
Z-score 3.80
OE 0.33 (0.210.53)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.67Z-score
OE missense 0.74 (0.670.83)
252 obs / 338.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.33 (0.210.53)
00.351.4
Missense OE0.74 (0.670.83)
00.61.4
Synonymous OE1.04
01.21.6
LoF obs/exp: 12 / 36.9Missense obs/exp: 252 / 338.3Syn Z: -0.33

ClinVar Variant Classifications

105 submitted variants in ClinVar

Classification Summary

Pathogenic14
VUS67
Likely Benign2
Benign1
14
Pathogenic
67
VUS
2
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
14
0
14
Likely Pathogenic
0
0
0
0
0
VUS
0
63
4
0
67
Likely Benign
0
1
0
1
2
Benign
0
0
1
0
1
Total06419184

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

View in ClinVar →

Protein Context — Lollipop Plot

KDM1B · 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
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Key Publications
Landmark & review papers · by relevance
PubMed
Top 2 results · since 2015Search PubMed ↗