IFT43

protein-coding

intraflagellar transport 43, the group of IFT-A complex

Gene summary

This gene encodes a subunit of the intraflagellar transport complex A (IFT-A). IFT-A is a multiprotein complex that plays an important role in cilia assembly and maintenance by mediating retrograde ciliary transport. Mutations in this gene are a cause of cranioectodermal dysplasia-3 (CED3), also known as Sensenbrenner syndrome. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

Previous symbols:

C14orf179

MANE transcript

NM_001102564.3

Inheritance

ClinVar variants

P:31U:94B:63

Top phenotype

Cranioectodermal dysplasia 3; Retinitis pigmentosa 81; Short-rib thoracic dysplasia 18 with polydactyly

gnomAD constraint

pLI —, LoF o/e 1.06

Max pathogenic AF

—

Genomic locus

chr14:75,902,136-76,084,585

External References & Databases

Ensembl (ENSG00000119650)

Transcript & Mutation Effects

hg38 • Region Span ~182.4 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

retinitis pigmentosa 81LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0036482

Submitter: Ambry Genetics

short-rib thoracic dysplasia 18 with polydactylySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0036483

Submitter: PanelApp Australia

retinitis pigmentosa 81LIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0036482

Submitter: Labcorp Genetics (formerly Invitae)

short-rib thoracic dysplasia 18 with polydactylySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0036483

Submitter: Labcorp Genetics (formerly Invitae)

retinitis pigmentosa 81STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0036482

Submitter: PanelApp Australia

retinitis pigmentosa 81LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0036482

Submitter: G2P

ciliopathyMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0005308

Submitter: ClinGen

*IFT43* was first reported in relation to autosomal recessive short-rib thoracic dysplasia and cranioectodermal dysplasia in 2011 (Arts et al., PMID: 21378380). Per criteria outlined by the ClinGen Lumping and Splitting Working Group, we found no difference in molecular mechanism and inheritance pattern. Therefore, the following disease entities have been lumped into one disease entity, Short-rib thoracic dysplasia 18 with polydactyly (OMIM:617866) and Cranioectodermal dysplasia 3 (OMIM:614099). Four variants (missense, start loss) have been reported in 5 probands in 4 publications (PMIDs: 28400947, 21378380, 29896747, 26489029) and are included in this curation. The mechanism of pathogenicity appears to be loss-of-function. This gene-disease relationship is also supported by experimental evidence (e.g. animal models, expression studies, in vitro functional assays, etc.; PMIDs: 28207750; doi:10.64898/2026.01.14.699321). This knockout mouse study demonstrated it causes a skeletal phenotype. Other experimental evidence reported (IP assays and rescue experiments) supported the ciliopathy. In summary, there is moderate evidence supporting the relationship between *IFT43* and autosomal recessive short-rib thoracic dysplasia and cranioectodermal dysplasia. This classification was approved by the ClinGen Skeletal Disorders GCEP on the meeting date April 22, 2026 (SOP Version 11).

cranioectodermal dysplasiaSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009032

Submitter: Orphanet

cranioectodermal dysplasia 3LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0013573

Submitter: G2P

cranioectodermal dysplasia 3STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013573

Submitter: PanelApp Australia

ciliopathyLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0005308

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Cranioectodermal dysplasia 3; Retinitis pigmentosa 81; Short-rib thoracic dysplasia 18 with polydactylyAR

Manifestation: Craniofacial; Dental; Dermatologic; Musculoskeletal; Neurologic; Ophthalmologic; Renal

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 21378380; 28400947; 28973684

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to IFT43 variants in ClinVar

11 Conditions Cataloged

not providedTotal: 267

Short-rib thoracic dysplasia 18 with polydactylyTotal: 78

Cranioectodermal dysplasia 3Total: 76

Retinitis pigmentosa 81Total: 75

not specifiedTotal: 54

IFT43-related disorderTotal: 10

Connective tissue disorderTotal: 4

Short rib-polydactyly syndromeTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001102564.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	52 clinvar		54
missense		3 clinvar	87 clinvar	9 clinvar	2 clinvar	101
nonsense	3 clinvar	5 clinvar	1 clinvar			9
start loss	3 clinvar					3
frameshift	3 clinvar	2 clinvar	1 clinvar			6
splice donor/acceptor (+/-2bp)		12 clinvar	3 clinvar			15
Total	9	22	94	61	2	188

Highest pathogenic variant AF is 0.0000954137

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 65 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001102564.3	RefSeq	NP_001096034.1	9	MANE Select
ENST00000314067.11	Ensembl	ENSP00000324177.6	9	MANE Select
NM_001255995.3	RefSeq	NP_001242924.1	4	Standard
NM_052873.3	RefSeq	NP_443105.2	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Intraflagellar transport
Cilium Assembly
Organelle biogenesis and maintenance

Biological Process

intraciliary retrograde transport
intraciliary transport involved in cilium assembly
cilium assembly

Molecular Function

protein binding

Cellular Component

cytoplasm
microtubule organizing center
cilium
microtubule cytoskeleton
intraciliary transport particle A

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000238628
Coding exons: 8
Length: 182450
Individuals with no LoFs: 125586
Homozygous LoFs: 0
Heterozygous LoFs: 162
Defined: 125748
p: 0.000644

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.296	132	123	1.08	0.00000792	1383
Missense (PolyPhen)		39	39.604	0.98476		451
Synonymous	-0.992	58	49.1	1.18	0.00000337	406
Loss of Function	-0.213	16	15.1	1.06	8.43e-7	158

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00031	0.00031	rare
Latino/Admixed American	0.00058	0.00058	rare
Ashkenazi Jewish	0.00099	0.00099	rare
East Asian	0.00033	0.00033	rare
Finnish	0.00037	0.00037	rare
European (Non-Finnish)	0.00067	0.00067	rare
South Asian	0.0011	0.0011	notable
Other	0.00049	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: As a component of IFT complex A (IFT-A), it is involved in ciliogenesis (PubMed:28400947, PubMed:28973684). Involved in retrograde ciliary transport along microtubules from the ciliary tip to the base (PubMed:21378380). {ECO:0000269|PubMed:21378380, ECO:0000269|PubMed:28400947, ECO:0000269|PubMed:28973684}.;
Disease: DISEASE: Retinitis pigmentosa 81 (RP81) [MIM:617871]: A form of retinitis pigmentosa, a retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. RP81 inheritance is autosomal recessive. {ECO:0000269|PubMed:28973684}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Short-rib thoracic dysplasia 18 with polydactyly (SRTD18) [MIM:617866]: A form of short-rib thoracic dysplasia, a group of autosomal recessive ciliopathies that are characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a 'trident' appearance of the acetabular roof. Polydactyly is variably present. Non-skeletal involvement can include cleft lip/palate as well as anomalies of major organs such as the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Some forms of the disease are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life. Disease spectrum encompasses Ellis-van Creveld syndrome, asphyxiating thoracic dystrophy (Jeune syndrome), Mainzer-Saldino syndrome, and short rib-polydactyly syndrome. {ECO:0000269|PubMed:28400947}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Intolerance Scores

RVIS EVS: -0.25
RVIS percentile EVS: 35.75

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.114

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium