RPGRIP1L

Chr 16AR

RPGRIP1 like

Also known as: COACH3, CORS3, FTM, JBTS7, MKS5, NPHP8, PPP1R134

NCBI Gene: 23322ENSG00000103494UniProt: Q68CZ1

The protein encoded by this gene can localize to the basal body-centrosome complex or to primary cilia and centrosomes in ciliated cells. The encoded protein has been found to interact with nephrocystin-4. Defects in this gene are a cause of Joubert syndrome type 7 (JBTS7) and Meckel syndrome type 5 (MKS5). [provided by RefSeq, Jun 2016]

Primary Disease Associations & Inheritance

?COACH syndrome 3MIM #619113
AR
Joubert syndrome 7MIM #611560
AR
Meckel syndrome 5MIM #611561
AR
587
ClinVar variants
98
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— RPGRIP1L
🧬
Gene-Disease Validity (ClinGen)
ciliopathy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
98 Pathogenic / Likely Pathogenic· 268 VUS of 587 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.96LOEUF
pLI 0.000
Z-score 1.86
OE 0.77 (0.62–0.96)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.11Z-score
OE missense 1.01 (0.95–1.08)
696 obs / 688.0 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.77 (0.62–0.96)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.01 (0.95–1.08)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.00
0≤1.21.6
LoF obs/exp: 57 / 74.3Missense obs/exp: 696 / 688.0Syn Z: -0.00

ClinVar Variant Classifications

587 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic40
Likely Pathogenic58
VUS268
Likely Benign211
Benign6
Conflicting4
40
Pathogenic
58
Likely Pathogenic
268
VUS
211
Likely Benign
6
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
20
0
20
0
40
Likely Pathogenic
39
4
15
0
58
VUS
0
237
22
9
268
Likely Benign
1
1
124
85
211
Benign
0
1
5
0
6
Conflicting
—4
Total6024318694587

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

View in ClinVar →

Protein Context — Lollipop Plot

RPGRIP1L · protein map & ClinVar variants

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

Gene2Phenotype Curations

RPGRIP1L-related Meckel syndrome

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersEyeSkeletal
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
RPGRIP1-LIKE; RPGRIP1L
MIM #610937 · *

?COACH syndrome 3

MIM #619113

Molecular basis of disorder known

Autosomal recessive

Joubert syndrome 7

MIM #611560

Molecular basis of disorder known

Autosomal recessive

Meckel syndrome 5

MIM #611561

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — RPGRIP1L
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Genotype-phenotype correlates in Joubert syndrome: A review.
Gana S et al.·Am J Med Genet C Semin Med Genet
2022Review
Clinical and genetic spectrum from a prototype of ciliopathy: Joubert syndrome.
Aksu Uzunhan T et al.·Clin Neurol Neurosurg
2023
Identification of Pathogenic Variants in RPGRIP1L with Meckel Syndrome and Preimplantation Genetic Testing in a Chinese Family.
Zhang P et al.·Reprod Sci
2022Case report
RPGRIP1L is required for stabilizing epidermal keratinocyte adhesion through regulating desmoglein endocytosis.
Choi YJ et al.·PLoS Genet
2019
Mutations in RPGRIP1L: extending the clinical spectrum of ciliopathies.
Devuyst O et al.·Nephrol Dial Transplant
2008Review
Novel mutation in RPGRIP1L gene causing Joubert syndrome: A case report.
Duque-Cordoba PA et al.·Medicine (Baltimore)
2023Case report
Joubert syndrome and related disorders.
Paprocka J et al.·Neurol Neurochir Pol
2012Review
A common allele in RPGRIP1L is a modifier of retinal degeneration in ciliopathies.
Khanna H et al.·Nat Genet
2009
[Clinical and genetic analyses of Joubert syndrome in children].
Zhang GY et al.·Zhongguo Dang Dai Er Ke Za Zhi
2023
Molecular genetics and pathogenic mechanisms for the severe ciliopathies: insights into neurodevelopment and pathogenesis of neural tube defects.
Logan CV et al.·Mol Neurobiol
2011Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Identification of RPGRIP1L as an instability-maintaining gene to drive tumor growth and PD-L1 expression via Hedgehog signaling in breast cancer.
Lv M et al.·BMC Cancer
2025🔓 Open Access
Production and characterisation of four Joubert syndrome patient-derived induced pluripotent stem cell (iPSC) lines with mutations in either RPGRIP1L or CPLANE1 genes.
Pollara L et al.·Stem Cell Res
2025
Downregulation of Hmox1 and Rpgrip1l Expression Linked to Risk-Taking Behavior, Reduced Depressive Symptoms, and Diminished Novelty Socialization in SUMO1 Knockout Mice.
Dai Q et al.·Cell Mol Neurobiol
2025🔓 Open Access
Case report: Successful PGT-M based on the identification of a spliceogenic variant in the RPGRIP1L gene through Minigene assay.
Xu H et al.·Front Genet
2024🔓 Open AccessCase report
RPGRIP1L as a new biomarker for prognosis and tumor immune of breast cancer.
Yi J et al.·FASEB J
2024
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools