B9D2

Chr 19AR

B9 domain containing 2

Also known as: ICIS-1, JBTS34, MKS10, MKSR-2, MKSR2

NCBI Gene: 80776 ENSG00000123810 UniProt: Q9BPU9 OMIM: 611951

The encoded protein is a component of the tectonic-like complex that localizes to the transition zone of primary cilia and acts as a barrier preventing diffusion of transmembrane proteins between cilia and plasma membranes. Mutations cause Meckel syndrome 10 and Joubert syndrome 34, both ciliopathies affecting multiple organ systems including the brain, kidneys, and liver. Inheritance is autosomal recessive.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a B9 domain protein, which are exclusively found in ciliated organisms. The gene is upregulated during mucociliary differentiation, and the encoded protein localizes to basal bodies and cilia. Disrupting expression of this gene results in ciliogenesis defects. [provided by RefSeq, Oct 2009]

GeneReviews OMIM ResearchGenerating clinical summary…

ARLOEUF 1.572 OMIM phenotypes

Clinical Summary— B9D2

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Gene-Disease Validity (ClinGen)

ciliopathy · ARModerate

Moderate evidence — consider for supplementary testing

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Population Constraint (gnomAD)

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

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ClinVar Variants

10 unique Pathogenic / Likely Pathogenic· 49 VUS of 110 total submissions

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GeneReview available — B9D2

Authoritative clinical overview · Recommended first read

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.57LOEUF

pLI 0.000

Z-score 0.38

OE 0.86 (0.48–1.57)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.13Z-score

OE missense 1.03 (0.89–1.20)

124 obs / 120.0 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.86 (0.48–1.57)

0≤0.351.4

Missense OE?1.03 (0.89–1.20)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 7 / 8.2Missense obs/exp: 124 / 120.0Syn Z: 0.17

ClinVar Variant Classifications

110 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2

Likely Pathogenic8

VUS49

Likely Benign36

Benign10

Conflicting1

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	2	0	0	2
Likely Pathogenic	5	3	0	0	8
VUS	1	45	3	0	49
Likely Benign	0	2	8	26	36
Benign	0	1	9	0	10
Conflicting	—				1
Total	6	53	20	26	106

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

View in ClinVar →

6 pathogenic / likely-pathogenic (of 8) ClinVar copy-number / structural variants overlap B9D2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →