B9D1

Chr 17AR

B9 domain containing 1

Also known as: B9, EPPB9, JBTS27, MKS9, MKSR-1, MKSR1

NCBI Gene: 27077ENSG00000108641UniProt: Q9UPM9

This gene encodes a B9 domain-containing protein, one of several that are involved in ciliogenesis. Alterations in expression of this gene have been found in a family with Meckel syndrome. Meckel syndrome has been associated with at least six different genes. This gene is located within the Smith-Magenis syndrome region on chromosome 17. [provided by RefSeq, Mar 2016]

Primary Disease Associations & Inheritance

?Meckel syndrome 9MIM #614209
AR
Joubert syndrome 27MIM #617120
AR
376
ClinVar variants
113
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— B9D1
🧬
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
113 Pathogenic / Likely Pathogenic· 122 VUS of 376 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.
0.95LOEUF
pLI 0.003
Z-score 1.69
OE 0.48 (0.26–0.95)
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.
0.10Z-score
OE missense 0.97 (0.84–1.13)
121 obs / 124.2 exp
Tolerant

Mild missense constraint

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.0.48 (0.26–0.95)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.97 (0.84–1.13)
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.1.11
0≤1.21.6
LoF obs/exp: 6 / 12.4Missense obs/exp: 121 / 124.2Syn Z: -0.58

ClinVar Variant Classifications

376 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic104
Likely Pathogenic9
VUS122
Likely Benign111
Benign18
Conflicting12
104
Pathogenic
9
Likely Pathogenic
122
VUS
111
Likely Benign
18
Benign
12
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
4
0
100
0
104
Likely Pathogenic
2
5
2
0
9
VUS
3
89
29
1
122
Likely Benign
2
11
51
47
111
Benign
0
1
17
0
18
Conflicting
—12
Total1110619948376

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

View in ClinVar →

Protein Context — Lollipop Plot

B9D1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

B9D1-related Meckel syndrome

strong
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

?Meckel syndrome 9

MIM #614209

Molecular basis of disorder known

Autosomal recessive

Joubert syndrome 27

MIM #617120

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — B9D1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Investigating the Role of B9D1 in Meckel-Gruber Syndrome: A Case Report and Comprehensive Literature Review.
Campobasso G et al.·Genes (Basel)
2025Review
Ciliopathy-related B9 protein complex regulates ciliary axonemal microtubule posttranslational modifications and initiation of ciliogenesis.
He R et al.·J Clin Invest
2025
B9D1 is revealed as a novel Meckel syndrome (MKS) gene by targeted exon-enriched next-generation sequencing and deletion analysis.
Hopp K et al.·Hum Mol Genet
2011
Two novel B9D1 variants causing Joubert syndrome: Utility of mRNA and splicing studies.
Katiyar D et al.·Eur J Med Genet
2020Case report
Joubert syndrome: genotyping a Northern European patient cohort.
Kroes HY et al.·Eur J Hum Genet
2016Cohort
Mutations in B9D1 and MKS1 cause mild Joubert syndrome: expanding the genetic overlap with the lethal ciliopathy Meckel syndrome.
Romani M et al.·Orphanet J Rare Dis
2014Case report
Exome survey of individuals affected by VATER/VACTERL with renal phenotypes identifies phenocopies and novel candidate genes.
Kolvenbach CM et al.·Am J Med Genet A
2021
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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