PROM1

Chr 4ADAR

prominin 1

Also known as: AC133, CD133, CORD12, MCDR2, MSTP061, PROML1, RP41, STGD4

The PROM1 protein is a pentaspan transmembrane glycoprotein that localizes to membrane protrusions, binds cholesterol in plasma membrane microdomains, and serves as a key regulator of retinal disk morphogenesis during early eye development. Mutations cause various forms of inherited retinal dystrophy including cone-rod dystrophy, Stargardt disease, retinitis pigmentosa, and macular dystrophy, primarily affecting vision through progressive degeneration of photoreceptors. The gene shows both autosomal dominant and autosomal recessive inheritance patterns and is not highly constrained against loss-of-function variants.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

Cone-rod dystrophy 12MIM #612657
ADAR
Macular dystrophy, retinal, 2MIM #608051
AD
Retinitis pigmentosa 41MIM #612095
AR
Stargardt disease 4MIM #603786
AD
0
Active trials
48
Pubs (1 yr)
0
P/LP submissions
P/LP missense
1.05
LOEUF
LOF
Mechanism· G2P
Clinical SummaryPROM1
🧬
Gene-Disease Validity (ClinGen)
PROM1-related dominant retinopathy · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

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

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.05LOEUF
pLI 0.000
Z-score 1.26
OE 0.80 (0.621.05)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.61Z-score
OE missense 1.08 (1.001.17)
478 obs / 441.8 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.80 (0.621.05)
00.351.4
Missense OE1.08 (1.001.17)
00.61.4
Synonymous OE0.99
01.21.6
LoF obs/exp: 39 / 48.5Missense obs/exp: 478 / 441.8Syn Z: 0.11
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitivePROM1-related macular dystrophyOTHERAD
definitivePROM1-related retinitis pigmentosaLOFAR
DN
0.6746th %ile
GOF
0.6932th %ile
LOF
0.2582th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). The Badonyi & Marsh model scores gain-of-function highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports dominant-negative. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median · 1 literature citation
GOFprediction 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.

Literature Evidence

DNFirst, we demonstrate that the overexpression of a dominant-negative mutant variant of human PROM1 (i.e. mutation Y819F/Y828F) significantly decreases ciliary length in Madin-Darby canine kidney cells.PMID:32201384

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

PROM1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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