KMT2D

Chr 12

lysine methyltransferase 2D

Also known as: AAD10, ALR, BCAHH, CAGL114, KABUK1, KMS, MLL2, MLL4

The protein encoded by this gene is a histone methyltransferase that methylates the Lys-4 position of histone H3. The encoded protein is part of a large protein complex called ASCOM, which has been shown to be a transcriptional regulator of the beta-globin and estrogen receptor genes. Mutations in this gene have been shown to be a cause of Kabuki syndrome. [provided by RefSeq, Oct 2010]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtKabuki syndrome 1
UniProtBranchial arch abnormalities, choanal atresia, athelia, hearing loss, and hypothyroidism syndrome

Clinical highlights

Gene-disease validity (ClinGen)
Kabuki syndrome 1 · ADDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.
5
Active trials
321
Pubs (1 yr)
P/LP submissions
P/LP missense
0.10
LOEUF· LoF intol.
LOF
Mechanism· G2P
📖
GeneReview available — KMT2D
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

Dual constrained — LoF & missense intolerant
LoF Constraint?
0.10LOEUF
pLI 1.000
Z-score 12.95
OE 0.07 (0.040.10)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?
3.73Z-score
OE missense 0.81 (0.790.84)
2541 obs / 3127.8 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?
LoF OE?0.07 (0.040.10)
00.351.4
Missense OE?0.81 (0.790.84)
00.61.4
Synonymous OE?1.05
01.21.6
LoF obs/exp: 15 / 224.4Missense obs/exp: 2541 / 3127.8Syn Z: -1.43

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

KMT2D · protein map & ClinVar variants

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