IFT172

Chr 2AR

intraflagellar transport 172

Also known as: BBS20, NPHP17, RP71, SLB, SRTD10, osm-1, wim

NCBI Gene: 26160 ENSG00000138002 UniProt: Q9UG01 OMIM: 607386

The protein is required for the maintenance and formation of cilia and plays an indirect role in hedgehog signaling. Mutations cause autosomal recessive ciliopathies including Bardet-Biedl syndrome, retinitis pigmentosa, and short-rib thoracic dysplasia with or without polydactyly. The gene is extremely intolerant to loss-of-function variants (pLI approaching 1), reflecting the critical importance of proper ciliary function for multiple organ systems including skeletal, retinal, and renal development.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a subunit of the intraflagellar transport subcomplex IFT-B. Subcomplexes IFT-A and IFT-B are necessary for ciliary assembly and maintenance. Mutations in this gene have been associated with skeletal ciliopathies, with or without polydactyly, such as such short-rib thoracic dysplasias 1, 9 or 10. [provided by RefSeq, Mar 2014]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.763 OMIM phenotypes

Clinical Summary— IFT172

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Gene-Disease Validity (ClinGen)

ciliopathy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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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

163 unique Pathogenic / Likely Pathogenic· 884 VUS of 2016 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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GeneReview available — IFT172

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.76LOEUF

pLI 0.000

Z-score 3.77

OE 0.62 (0.51–0.76)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.19Z-score

OE missense 0.89 (0.85–0.94)

892 obs / 997.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.62 (0.51–0.76)

0≤0.351.4

Missense OE?0.89 (0.85–0.94)

0≤0.61.4

Synonymous OE?0.92

0≤1.21.6

LoF obs/exp: 71 / 114.6Missense obs/exp: 892 / 997.4Syn Z: 1.27

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveIFT172-related short-rib thoracic dysplasia with or without polydactylyLOFAR

This gene — mechanism propensity

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

0.6355th %ile

GOF

0.5170th %ile

LOF

0.3452th %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

2016 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic76

Likely Pathogenic87

VUS884

Likely Benign802

Benign48

Conflicting92

Pathogenic

Likely Pathogenic

884

VUS

802

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	62	5	9	0	76
Likely Pathogenic	81	4	2	0	87
VUS	9	806	59	10	884
Likely Benign	1	11	394	396	802
Benign	0	6	39	3	48
Conflicting	—				92
Total	153	832	503	409	1,989

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

View in ClinVar →

15 pathogenic / likely-pathogenic (of 19) ClinVar copy-number / structural variants overlap IFT172 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →