RP1L1

Chr 8ADAR

RP1 like 1

Also known as: DCDC4B, OCMD, RP88

NCBI Gene: 94137 ENSG00000183638 UniProt: Q8IWN7 OMIM: 608581

The protein contains doublecortin domains that bind and regulate microtubule polymerization and is required for photoreceptor cell differentiation and organization of rod and cone outer segments in the retina. Mutations cause occult macular dystrophy and retinitis pigmentosa 88 with both autosomal dominant and autosomal recessive inheritance patterns. The gene shows very low constraint against loss-of-function variants, suggesting tolerance to such changes in the general population.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the doublecortin family. The protein encoded by this gene contains two N-terminal doublecortin domains, which bind microtubules and regulate microtubule polymerization, and two C-terminal large repetitive regions, both of which contain a high percentage of glutamine and glutamic acid residues. This protein is a retinal-specific protein. Its exact length varies among individuals due to the presence of a 16aa repeat in the first C-terminal repetitive region. The 16aa repeat is encoded by the highly polymorphic 48-bp repeat, and 1-6 copies of the 16aa repeat have been identified in normal individuals. The current reference sequence shown here has a single copy of the 16aa repeat. This protein and the RP1 protein, another retinal-specific protein, play essential and synergistic roles in affecting photosensitivity and outer segment morphogenesis of rod photoreceptors. Mutations in this gene cause occult macular dystrophy (OMD). [provided by RefSeq, Sep 2010]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Occult macular dystrophyMIM #613587

Retinitis pigmentosa 88MIM #618826

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · occult macular dystrophy · AD · ClinGen 2026

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.95

LOEUF

LOF

Mechanism· G2P

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.95LOEUF

pLI 0.000

Z-score -1.76

OE 1.72 (1.03–1.95)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-10.07Z-score

OE missense 1.77 (1.71–1.83)

2394 obs / 1351.9 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.72 (1.03–1.95)

0≤0.351.4

Missense OE?1.77 (1.71–1.83)

0≤0.61.4

Synonymous OE?1.51

0≤1.21.6

LoF obs/exp: 12 / 7.0Missense obs/exp: 2394 / 1351.9Syn Z: -9.81

Background carrier burden — how many people carry a rare variant somewhere in RP1L1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 9

5,144 rare PASS variants

Rare truncating (LoF)

1 in 50

666 rare PASS variants

Rare synonymous (reference)

1 in 18

1,917 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for RP1L1. 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 13	1 in 70
South Asian	~43k	1 in 8	1 in 63
Remaining (unassigned)	~30k	1 in 7	1 in 63
European (Finnish)	~27k	1 in 19	1 in 120
Admixed American	~22k	1 in 8	1 in 65
African / African American	~21k	1 in 8	1 in 42
East Asian	~20k	1 in 9	1 in 52
Ashkenazi Jewish	~13k	1 in 38	1 in 210
Middle Eastern	~2,884	1 in 8	1 in 100

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 3 coding exons well covered in gnomAD exomes and genomes.? see exons ↓