KIDINS220

kinase D interacting substrate 220, the group of Ankyrin repeat domain containing

Basic information

Region (hg38): 2:8721081-8837630

Links

ENSG00000134313

∙ NCBI:57498 ∙ OMIM:615759 ∙ HGNC:29508 ∙ Uniprot:Q9ULH0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

spastic paraplegia, intellectual disability, nystagmus, and obesity (Strong), mode of inheritance: AD
spastic paraplegia, intellectual disability, nystagmus, and obesity (Supportive), mode of inheritance: AD
ventriculomegaly and arthrogryposis (Strong), mode of inheritance: AR
spastic paraplegia, intellectual disability, nystagmus, and obesity (Strong), mode of inheritance: AD
ventriculomegaly and arthrogryposis (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spastic paraplegia, intellectual disability, nystagmus, and obesity (SINO); Ventriculomegaly and arthrogryposis	AR	General	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	Cardiovascular; Craniofacial; Endocrine; Musculoskeletal; Neurologic; Ophthalmologic	27005418; 28934391; 32909676; 33205811

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KIDINS220 gene.

not_provided (724 variants)
KIDINS220-related_disorder (420 variants)
Inborn_genetic_diseases (170 variants)
Spastic_paraplegia,_intellectual_disability,_nystagmus,_and_obesity (64 variants)
Ventriculomegaly_and_arthrogryposis (24 variants)
not_specified (21 variants)
Intellectual_disability (2 variants)
Obesity (1 variants)
Cerebral_palsy (1 variants)
See_cases (1 variants)
KCNA1-related_disorder (1 variants)
Hereditary_spastic_paraplegia (1 variants)
Kabuki_syndrome_1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KIDINS220 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000020738.4. 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	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			4 clinvar	248 clinvar	7 clinvar	259
missense	2 clinvar	1 clinvar	512 clinvar	52 clinvar	3 clinvar	570
nonsense	10 clinvar	7 clinvar	7 clinvar			24
start loss						0
frameshift	13 clinvar	17 clinvar	11 clinvar			41
splice donor/acceptor (+/-2bp)		5 clinvar	16 clinvar	2 clinvar		23
Total	25	30	550	302	10

Highest pathogenic variant AF is 0.000015488873

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KIDINS220	protein_coding	protein_coding	ENST00000256707	29	112353

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0736	0.926	124725	0	70	124795	0.000280

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.26	780	979	0.797	0.0000528	11608
Missense in Polyphen		271	419.05	0.6467		5196
Synonymous	0.222	362	367	0.985	0.0000213	3451
Loss of Function	6.41	20	83.0	0.241	0.00000444	1018

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00198	0.00194
Ashkenazi Jewish	0.0000993	0.0000993
East Asian	0.000287	0.000278
Finnish	0.0000475	0.0000464
European (Non-Finnish)	0.000224	0.000221
Middle Eastern	0.000287	0.000278
South Asian	0.000131	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Promotes a prolonged MAP-kinase signaling by neurotrophins through activation of a Rap1-dependent mechanism. Provides a docking site for the CRKL-C3G complex, resulting in Rap1-dependent sustained ERK activation. May play an important role in regulating postsynaptic signal transduction through the syntrophin-mediated localization of receptor tyrosine kinases such as EPHA4. In cooperation with SNTA1 can enhance EPHA4-induced JAK/STAT activation. Plays a role in nerve growth factor (NGF)- induced recruitment of RAPGEF2 to late endosomes and neurite outgrowth. May play a role in neurotrophin- and ephrin-mediated neuronal outgrowth and in axon guidance during neural development and in neuronal regeneration (By similarity). Modulates stress- induced apoptosis of melanoma cells via regulation of the MEK/ERK signaling pathway. {ECO:0000250, ECO:0000269|PubMed:18089783}.;
Disease: DISEASE: Spastic paraplegia, intellectual disability, nystagmus, and obesity (SINO) [MIM:617296]: An autosomal dominant syndrome characterized by rapid growth in infancy, obesity, global developmental delay, intellectual disability, spastic paraplegia, ocular defects, and dysmorphic facial features. {ECO:0000269|PubMed:27005418}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Neurotrophin signaling pathway - Homo sapiens (human);Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;Signal Transduction;ARMS-mediated activation;Prolonged ERK activation events;Signalling to ERKs;Signaling by NTRK1 (TRKA);Signaling by NTRKs;Signaling by Receptor Tyrosine Kinases (Consensus)

Recessive Scores

pRec: 0.588

Intolerance Scores

loftool: 0.623
rvis_EVS: -2.25
rvis_percentile_EVS: 1.3

Haploinsufficiency Scores

pHI
hipred: Y
hipred_score: 0.694
ghis: 0.675

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.905

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Kidins220
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); 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); vision/eye phenotype; growth/size/body region phenotype; cellular phenotype;

Gene ontology

Biological process: activation of MAPKK activity;in utero embryonic development;positive regulation of neuron projection development;nerve growth factor signaling pathway;dendrite morphogenesis;cellular response to nerve growth factor stimulus
Cellular component: late endosome;cytosol;membrane;integral component of membrane;protein-containing complex
Molecular function: protein kinase regulator activity;PDZ domain binding