RETNLB

Chr 3

resistin like beta

Also known as: FIZZ1, FIZZ2, HXCP2, RELM-beta, RELMb, RELMbeta, XCP2

NCBI Gene: 84666 ENSG00000163515 UniProt: Q9BQ08 OMIM: 605645

The protein functions as a hormone involved in epithelial cell proliferation and is active in the extracellular space. Mutations in this gene have not been established to cause any recognized Mendelian diseases in current medical literature. The gene shows low constraint against loss-of-function variants (pLI 0.04, LOEUF 1.74), suggesting tolerance to such mutations.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable hormone activity. Involved in epithelial cell proliferation. Predicted to be located in extracellular region. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.74

Clinical Summary— RETNLB

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Population Constraint (gnomAD)

Low constraint (pLI 0.04) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

19 VUS of 22 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.74LOEUF

pLI 0.043

Z-score 0.52

OE 0.67 (0.27–1.74)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.25Z-score

OE missense 1.09 (0.90–1.33)

68 obs / 62.3 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.67 (0.27–1.74)

0≤0.351.4

Missense OE?1.09 (0.90–1.33)

0≤0.61.4

Synonymous OE?1.06

0≤1.21.6

LoF obs/exp: 2 / 3.0Missense obs/exp: 68 / 62.3Syn Z: -0.24

This gene — mechanism propensity

0.6936th %ile

GOF

0.4777th %ile

LOF

0.2483th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

22 submitted variants in ClinVar

ClinVar

Classification Summary

VUS19

Likely Benign2

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	19	19
Likely Benign	2	2
Benign	0	0
Total	21	21

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

View in ClinVar →

16 pathogenic / likely-pathogenic (of 20) ClinVar copy-number / structural variants overlap RETNLB — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →