GLOD4

Chr 17

glyoxalase domain containing 4

Also known as: C17orf25, CGI-150, HC6, HC71

NCBI Gene: 51031 ENSG00000167699 UniProt: Q9HC38 OMIM: 620650

The protein enables cadherin binding activity and is located in extracellular exosomes and mitochondria. Mutations in this gene cause autosomal recessive developmental and epileptic encephalopathy with microcephaly. This gene is not highly constrained against loss-of-function variants, consistent with a recessive inheritance pattern.

OMIM ResearchSummary from RefSeq

Enables cadherin binding activity. Located in extracellular exosome and mitochondrion. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.59

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.59LOEUF

pLI 0.000

Z-score -0.30

OE 1.08 (0.74–1.59)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.01Z-score

OE missense 1.00 (0.88–1.13)

168 obs / 168.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.08 (0.74–1.59)

0≤0.351.4

Missense OE?1.00 (0.88–1.13)

0≤0.61.4

Synonymous OE?1.11

0≤1.21.6

LoF obs/exp: 18 / 16.7Missense obs/exp: 168 / 168.3Syn Z: -0.68

Background carrier burden — how many people carry a rare variant somewhere in GLOD4?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 120

469 rare PASS variants

Rare truncating (LoF)

1 in 1,500

103 rare PASS variants

Rare synonymous (reference)

1 in 170

168 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for GLOD4. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 140	1 in 2,000
South Asian	~43k	1 in 110	1 in 2,200
Remaining (unassigned)	~30k	1 in 100	1 in 2,500
European (Finnish)	~27k	1 in 350	≈ 1 in 13,000
Admixed American	~22k	1 in 90	1 in 930
African / African American	~21k	1 in 110	1 in 370
East Asian	~20k	1 in 120	1 in 1,300
Ashkenazi Jewish	~13k	1 in 390	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 120	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 3 of 9 coding exons well covered in gnomAD exomes; exons 2, 5, 6, 7, 8, 9 marginal. Genomes: all 9.? see exons ↓