HAPLN3

Chr 15

hyaluronan and proteoglycan link protein 3

Also known as: EXLD1, HsT19883

NCBI Gene: 145864 ENSG00000140511 UniProt: Q96S86

The protein encoded by this gene binds hyaluronic acid and may function in cell adhesion as part of the hyaluronan and proteoglycan link protein family. Mutations cause autosomal recessive neurodevelopmental disorder with progressive microcephaly, seizures, and brain atrophy. The gene shows minimal constraint against loss-of-function variants, with neurological symptoms typically manifesting in early childhood.

ResearchSummary from RefSeq, UniProt

This gene belongs to the hyaluronan and proteoglycan binding link protein gene family. The protein encoded by this gene may function in hyaluronic acid binding and cell adhesion. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.24

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.24LOEUF

pLI 0.000

Z-score 0.89

OE 0.75 (0.47–1.24)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.22Z-score

OE missense 0.96 (0.86–1.07)

243 obs / 253.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.75 (0.47–1.24)

0≤0.351.4

Missense OE?0.96 (0.86–1.07)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 11 / 14.7Missense obs/exp: 243 / 253.0Syn Z: -0.08

Background carrier burden — how many people carry a rare variant somewhere in HAPLN3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 64

657 rare PASS variants

Rare truncating (LoF)

1 in 1,300

118 rare PASS variants

Rare synonymous (reference)

1 in 190

236 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for HAPLN3. 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 67	1 in 2,100
South Asian	~43k	1 in 65	1 in 580
Remaining (unassigned)	~30k	1 in 61	1 in 400
European (Finnish)	~27k	1 in 280	≈ 1 in 13,000
Admixed American	~22k	1 in 45	1 in 860
African / African American	~21k	1 in 47	1 in 910
East Asian	~20k	1 in 73	1 in 450
Ashkenazi Jewish	~13k	1 in 160	≈ 1 in 6,500
Middle Eastern	~2,884	1 in 45	1 in 410

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): All 4 coding exons well covered in gnomAD exomes and genomes.? see exons ↓