GORAB

Chr 1AR

golgin, RAB6 interacting

Also known as: GO, NTKLBP1, SCYL1BP1

The protein is a golgin family member that localizes to the Golgi apparatus and functions in the secretory pathway, with additional cytoplasmic localization suggesting a role in mitosis. Mutations cause geroderma osteodysplasticum, a rare connective tissue disorder affecting skin and bone development, inherited in an autosomal recessive pattern. The gene shows minimal constraint against loss-of-function variants (pLI near 0, LOEUF ~1.0), consistent with its recessive inheritance pattern.

Summary from RefSeq, OMIM
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Primary Disease Associations & Inheritance

Geroderma osteodysplasticumMIM #231070
AR
0
Active trials
3
Pubs (1 yr)
96
P/LP submissions
3%
P/LP missense
0.99
LOEUF
LOF
Mechanism· G2P
Clinical SummaryGORAB
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Gene-Disease Validity (ClinGen)
geroderma osteodysplastica · 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.
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ClinVar Variants
75 unique Pathogenic / Likely Pathogenic· 168 VUS of 457 total submissions
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GeneReview available — GORAB
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.99LOEUF
pLI 0.000
Z-score 1.61
OE 0.60 (0.370.99)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.18Z-score
OE missense 1.03 (0.931.16)
223 obs / 215.6 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.60 (0.370.99)
00.351.4
Missense OE1.03 (0.931.16)
00.61.4
Synonymous OE1.16
01.21.6
LoF obs/exp: 11 / 18.4Missense obs/exp: 223 / 215.6Syn Z: -1.09
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveGORAB-related geroderma osteodysplasticumLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.80top 25%
GOF
0.74top 25%
LOF
0.2775th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

457 submitted variants in ClinVar

Classification Summary

Pathogenic62
Likely Pathogenic13
VUS168
Likely Benign170
Benign26
Conflicting10
62
Pathogenic
13
Likely Pathogenic
168
VUS
170
Likely Benign
26
Benign
10
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
18
1
43
0
62
Likely Pathogenic
9
1
3
0
13
VUS
1
117
50
0
168
Likely Benign
0
5
56
109
170
Benign
0
1
21
4
26
Conflicting
10
Total28125173113449

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

View in ClinVar →

Protein Context — Lollipop Plot

GORAB · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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