KDM7A

protein-coding

lysine demethylase 7A, the group of PHD finger proteins|Lysine demethylases

Gene summary

Enables histone demethylase activity and transition metal ion binding activity. Predicted to be involved in chromatin remodeling; midbrain development; and regulation of transcription by RNA polymerase II. Predicted to be located in nucleoplasm. Implicated in melanoma. [provided by Alliance of Genome Resources, Jun 2026]

Previous symbols:

JHDM1D

MANE transcript

NM_030647.2

Inheritance

ClinVar variants

U:89B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.12

Max pathogenic AF

—

Genomic locus

chr7:140,084,746-140,176,983

External References & Databases

Ensembl (ENSG00000006459)

Transcript & Mutation Effects

hg38 • Region Span ~92.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

cerebral palsyLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0006497

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to KDM7A variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 89

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_030647.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				1 clinvar		1
missense			89 clinvar			89
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	89	1	0	90

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 14 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_030647.2	RefSeq	NP_085150.1	20	MANE Select
ENST00000397560.7	Ensembl	ENSP00000380692.2	20	MANE Select
ENST00000472616.1	Ensembl	ENSP00000420143.1	10	Standard
ENST00000895776.1	Ensembl	ENSP00000565835.1	18	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Disease
HDMs demethylate histones
Chromatin modifying enzymes
Chromatin organization
Signaling by BRAF and RAF fusions

Biological Process

midbrain development
histone H3-K9 demethylation
histone H4-K20 demethylation
positive regulation of transcription, DNA-templated
oxidation-reduction process

Molecular Function

iron ion binding
zinc ion binding
2-oxoglutarate-dependent dioxygenase activity
histone demethylase activity
histone demethylase activity (H3-K9 specific)

Cellular Component

nucleus
nucleoplasm
nucleolus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000397560
Coding exons: 20
Length: 92290
Individuals with no LoFs: 124783
Homozygous LoFs: 0
Heterozygous LoFs: 11
Defined: 124794
p: 0.0000441

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.46	334	487	0.686	0.0000240	6217
Missense (PolyPhen)		73	178.6	0.40874		2274
Synonymous	0.175	169	172	0.983	0.00000878	1718
Loss of Function	5.89	6	51.7	0.116	0.00000277	626

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000030	0.000029	rare
Ashkenazi Jewish	0.00011	0.000099	rare
East Asian	0	0.0	absent
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.000045	0.000044	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Histone demethylase required for brain development. Specifically demethylates dimethylated 'Lys-9' and 'Lys-27' (H3K9me2 and H3K27me2, respectively) of histone H3 and monomethylated histone H4 'Lys-20' residue (H4K20Me1), thereby playing a central role in histone code. Specifically binds trimethylated 'Lys-4' of histone H3 (H3K4me3), affecting histone demethylase specificity: in presence of H3K4me3, it has no demethylase activity toward H3K9me2, while it has high activity toward H3K27me2. Demethylates H3K9me2 in absence of H3K4me3. Has activity toward H4K20Me1 only when nucleosome is used as a substrate and when not histone octamer is used as substrate. {ECO:0000269|PubMed:20023638, ECO:0000269|PubMed:20194436, ECO:0000269|PubMed:20622853}.;

Recessive Scores

pRec: 0.0936

Intolerance Scores

RVIS EVS: -0.18
RVIS percentile EVS: 40.56

Essentials

Essential (gene trap): N

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium