INSL5

Chr 1

insulin like 5

Also known as: PRO182, UNQ156

NCBI Gene: 10022 ENSG00000172410 UniProt: Q9Y5Q6 OMIM: 606413

The encoded protein is a hormone similar to relaxin that activates the RXFP4 receptor and may regulate gut contractility and thymic development. Mutations cause autosomal recessive developmental and epileptic encephalopathy with microcephaly and simplified gyral pattern, typically presenting in early infancy. This gene shows low constraint to loss-of-function variation in the general population.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene contains a classical signature of the insulin superfamily and is highly similar to relaxin 3 (RLN3/INSL7). [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.78

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.78LOEUF

pLI 0.136

Z-score 0.57

OE 0.55 (0.18–1.78)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.05Z-score

OE missense 1.02 (0.84–1.23)

76 obs / 74.7 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.55 (0.18–1.78)

0≤0.351.4

Missense OE?1.02 (0.84–1.23)

0≤0.61.4

Synonymous OE?0.87

0≤1.21.6

LoF obs/exp: 1 / 1.8Missense obs/exp: 76 / 74.7Syn Z: 0.50

Background carrier burden — how many people carry a rare variant somewhere in INSL5?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 250

183 rare PASS variants

Rare truncating (LoF)

1 in 2,600

39 rare PASS variants

Rare synonymous (reference)

1 in 1,300

73 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for INSL5. 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 380	1 in 3,300
South Asian	~43k	1 in 250	≈ 1 in 14,000
Remaining (unassigned)	~30k	1 in 230	1 in 3,000
European (Finnish)	~27k	1 in 560	1 in 1,500
Admixed American	~22k	1 in 120	1 in 3,700
African / African American	~21k	1 in 200	1 in 1,200
East Asian	~20k	1 in 190	1 in 760
Ashkenazi Jewish	~13k	1 in 2,600	none seen
Middle Eastern	~2,884	1 in 360	≈ 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): All 2 coding exons well covered in gnomAD exomes and genomes.? see exons ↓