JMJD8

Chr 16

jumonji domain containing 8

Also known as: C16orf20, PP14397

NCBI Gene: 339123 ENSG00000161999 UniProt: Q96S16

JMJD8 encodes a protein that regulates TNF-induced NF-kappaB signaling and controls angiogenesis and cellular metabolism through interaction with pyruvate kinase. Mutations cause autosomal recessive intellectual developmental disorder with seizures and language delay, with onset in early childhood. The gene shows low constraint against loss-of-function variants, consistent with recessive inheritance.

ResearchSummary from RefSeq, UniProt

Predicted to enable cis-regulatory region sequence-specific DNA binding activity. Involved in several processes, including positive regulation of canonical NF-kappaB signal transduction; positive regulation of sprouting angiogenesis; and regulation of pyruvate kinase activity. Located in endoplasmic reticulum lumen and nucleus. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

LOEUF 1.81

Clinical Summary— JMJD8

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

25 unique Pathogenic / Likely Pathogenic· 162 VUS of 276 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.81LOEUF

pLI 0.000

Z-score -0.95

OE 1.27 (0.88–1.81)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-1.92Z-score

OE missense 1.43 (1.28–1.60)

224 obs / 156.3 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.27 (0.88–1.81)

0≤0.351.4

Missense OE?1.43 (1.28–1.60)

0≤0.61.4

Synonymous OE?1.55

0≤1.21.6

LoF obs/exp: 18 / 14.1Missense obs/exp: 224 / 156.3Syn Z: -3.61

ClinVar Variant Classifications

276 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4

Likely Pathogenic21

VUS162

Likely Benign47

Benign7

Conflicting7

Pathogenic

Likely Pathogenic

162

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	2	2	0	0	4
Likely Pathogenic	15	5	1	0	21
VUS	5	144	13	0	162
Likely Benign	0	4	22	21	47
Benign	0	0	7	0	7
Conflicting	—				7
Total	22	155	43	21	248

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

View in ClinVar →

48 pathogenic / likely-pathogenic (of 72) ClinVar copy-number / structural variants overlap JMJD8 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →