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

ENSG00000164066NCBI:27152OMIM:610621HGNC:29239Uniprot:Q9ULD6AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

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

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Orofaciodigital syndrome XVII; Short-rib thoracic dysplasia 20 with polydactylyARCardiovascularThe condition can involve congenital cardiac anomalies, and awareness may allow early managementCardiovascular; Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Pulmonary27158779

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.

EffectPLPVUSLBBSum
synonymous
2
clinvar
56
clinvar
2
clinvar
60
missense
3
clinvar
215
clinvar
13
clinvar
7
clinvar
238
nonsense
3
clinvar
6
clinvar
9
start loss
0
frameshift
2
clinvar
3
clinvar
8
clinvar
13
splice donor/acceptor (+/-2bp)
2
clinvar
2
Total 2 9 233 69 9

Highest pathogenic variant AF is 0.000061342624

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
INTUprotein_codingprotein_codingENST00000335251 16103467
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
7.70e-100.9991256630841257470.000334
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.3844634870.9510.00002456144
Missense in Polyphen103118.170.871651601
Synonymous1.171591790.8890.000009181816
Loss of Function2.912242.50.5180.00000197567

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.001200.000945
Ashkenazi Jewish0.00009930.0000992
East Asian0.0003330.000326
Finnish0.000.00
European (Non-Finnish)0.0004150.000413
Middle Eastern0.0003330.000326
South Asian0.0002290.000229
Other0.0003270.000326

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

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

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