INTU

inturned planar cell polarity protein, the group of Ciliogenesis and planar polarity effector complex subunits|PDZ domain containing

Basic information

Region (hg38): 4:127623271-127726737

Previous symbols: [ "PDZK6", "PDZD6" ]

Links

ENSG00000164066 ∙ NCBI:27152 ∙ OMIM:610621 ∙ HGNC:29239 ∙ Uniprot:Q9ULD6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• orofaciodigital syndrome 17 (Moderate), mode of inheritance: AR
• orofaciodigital syndrome 17 (Limited), mode of inheritance: Unknown
• short-rib thoracic dysplasia 20 with polydactyly (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Orofaciodigital syndrome XVII; Short-rib thoracic dysplasia 20 with polydactyly	AR	Cardiovascular	The condition can involve congenital cardiac anomalies, and awareness may allow early management	Cardiovascular; Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Pulmonary	27158779

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the INTU gene.

• not_provided (309 variants)
• Inborn_genetic_diseases (99 variants)
• INTU-related_disorder (19 variants)
• Orofaciodigital_syndrome_17 (8 variants)
• Short-rib_thoracic_dysplasia_20_with_polydactyly (8 variants)
• Short_rib-polydactyly_syndrome (2 variants)
• not_specified (2 variants)
• Jeune_thoracic_dystrophy (2 variants)
• Nephronophthisis (1 variants)
• Growth_delay (1 variants)
• Short-rib_thoracic_dysplasia_7/20_with_polydactyly,_digenic (1 variants)
• EBV-positive_nodal_T-_and_NK-cell_lymphoma (1 variants)
• Mohr_syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the INTU gene is commonly pathogenic or not. These statistics are base on transcript: NM_000015693.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	56	2	60
missense		3	215	13	7	238
nonsense		3	6			9
start loss						0
frameshift	2	3	8			13
splice donor/acceptor (+/-2bp)			2			2
Total	2	9	233	69	9

Highest pathogenic variant AF is 0.000061342624

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
INTU	protein_coding	protein_coding	ENST00000335251	16	103467

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
7.70e-10	0.999	125663	0	84	125747	0.000334

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.384	463	487	0.951	0.0000245	6144
Missense in Polyphen		103	118.17	0.87165		1601
Synonymous	1.17	159	179	0.889	0.00000918	1816
Loss of Function	2.91	22	42.5	0.518	0.00000197	567

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00120	0.000945
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.000333	0.000326
Finnish	0.00	0.00
European (Non-Finnish)	0.000415	0.000413
Middle Eastern	0.000333	0.000326
South Asian	0.000229	0.000229
Other	0.000327	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays a key role in ciliogenesis and embryonic development. Regulator of cilia formation by controlling the organization of the apical actin cytoskeleton and the positioning of the basal bodies at the apical cell surface, which in turn is essential for the normal orientation of elongating ciliary microtubules. Plays a key role in definition of cell polarity via its role in ciliogenesis but not via conversion extension. Has an indirect effect on hedgehog signaling (By similarity). Proposed to function as core component of the CPLANE (ciliogenesis and planar polarity effectors) complex involved in the recruitment of peripheral IFT-A proteins to basal bodies (PubMed:27158779). {ECO:0000250|UniProtKB:Q059U7, ECO:0000250|UniProtKB:Q2I0E5, ECO:0000305|PubMed:27158779}.
• Disease: DISEASE: Short-rib thoracic dysplasia 20 with polydactyly (SRTD20) [MIM:617925]: 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:27158779}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Orofaciodigital syndrome 17 (OFD17) [MIM:617926]: A form of orofaciodigital syndrome, a group of heterogeneous disorders characterized by malformations of the oral cavity, face and digits, and associated phenotypic abnormalities that lead to the delineation of various subtypes. OFD17 inheritance is autosomal recessive. {ECO:0000269|PubMed:27158779}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Short-rib thoracic dysplasia 7/20 with polydactyly, digenic (SRTD7/20) [MIM:614091]: A digenic form of short-rib thoracic dysplasia caused by double heterozygosity for a mutation in the WDR35 gene and a mutation in the INTU gene. Short-rib thoracic dysplasia is part of a group of 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. Note=The disease is caused by mutations affecting distinct genetic loci, including the gene represented in this entry. SRTD7/20 can be caused by co-occurrence of WDR35 variant p.Trp311Leu and INTU p.Gln276Ter. One such patient has been reported. {ECO:0000269|PubMed:27158779}.

Recessive Scores

• pRec: 0.223

Intolerance Scores

• loftool: 0.189
• rvis_EVS: -0.53
• rvis_percentile_EVS: 20.89

Haploinsufficiency Scores

• pHI: 0.105
• hipred: N
• hipred_score: 0.492
• ghis: 0.537

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.177

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Intu
• Phenotype: skeleton phenotype; renal/urinary system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); limbs/digits/tail phenotype; vision/eye phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; embryo phenotype; homeostasis/metabolism phenotype; cellular phenotype; growth/size/body region phenotype

Gene ontology

• Biological process: establishment of planar polarity;nervous system development;regulation of smoothened signaling pathway;negative regulation of keratinocyte proliferation;spinal cord dorsal/ventral patterning;neural tube development;keratinocyte differentiation;regulation of ossification;hair follicle morphogenesis;embryonic digit morphogenesis;motile cilium assembly;positive regulation of smoothened signaling pathway;negative regulation of cell division;limb development;cilium assembly;non-motile cilium assembly
• Cellular component: cytoplasm;cell surface;motile cilium;ciliary basal body
• Molecular function: protein binding