KIRREL3

kirre like nephrin family adhesion molecule 3, the group of I-set domain containing|C2-set domain containing|MicroRNA protein coding host genes

Basic information

Region (hg38): 11:126423358-127003460

Links

ENSG00000149571

∙ NCBI:84623 ∙ OMIM:607761 ∙ HGNC:23204 ∙ Uniprot:Q8IZU9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

intellectual disability, autosomal dominant 4 (Limited), mode of inheritance: AD
autosomal dominant non-syndromic intellectual disability (Supportive), mode of inheritance: AD
intellectual disability, autosomal dominant 4 (Limited), mode of inheritance: Unknown
complex neurodevelopmental disorder (Disputed Evidence), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mental retardation, autosomal dominant 4	AD	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	Craniofacial; Musculoskeletal; Neurologic	19012874

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KIRREL3 gene.

not_specified (111 variants)
not_provided (43 variants)
KIRREL3-related_disorder (18 variants)
Intellectual_disability,_autosomal_dominant_4 (6 variants)
Autism_spectrum_disorder (2 variants)
Difficulty_walking (1 variants)
Global_developmental_delay (1 variants)
Absent_speech (1 variants)
Thoracic_scoliosis (1 variants)
Intellectual_disability (1 variants)
Developmental_disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KIRREL3 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000032531.4. 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			3 clinvar	31 clinvar	6 clinvar	40
missense		2 clinvar	95 clinvar	9 clinvar	2 clinvar	108
nonsense			1 clinvar	1 clinvar		2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)		1 clinvar				1
Total	0	3	99	41	8

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KIRREL3	protein_coding	protein_coding	ENST00000525144	17	580102

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.970	0.0301	124734	0	10	124744	0.0000401

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.35	343	490	0.701	0.0000321	4990
Missense in Polyphen		127	212.85	0.59666		2098
Synonymous	0.745	200	214	0.935	0.0000160	1559
Loss of Function	4.75	6	37.3	0.161	0.00000185	424

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000117	0.0000965
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000642	0.0000619
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Synaptic adhesion molecule required for the formation of target-specific synapses. Required for formation of target- specific synapses at hippocampal mossy fiber synapses. Required for formation of mossy fiber filopodia, the synaptic structures connecting dentate granule and GABA neurons. Probably acts as a homophilic adhesion molecule that promotes trans-cellular interactions and stabilize mossy fiber filipodia contact and subsequent synapse formation. Required for the coalescence of vomeronasal sensory neuron axons. May be involved in the hematopoietic supportive capacity of stroma cells; the secreted extracellular domain is directly responsible for supporting hematopoietic stem cells. {ECO:0000250|UniProtKB:Q8BR86}.;
Disease: DISEASE: Note=A chromosomal aberration involving KIRREL3 and CDH15 is found in a patient with severe mental retardation and dysmorphic facial features. Translocation t(11;16)(q24.2;q24). {ECO:0000269|PubMed:19012874}.;
Pathway: Primary Focal Segmental Glomerulosclerosis FSGS;Nephrin family interactions;Cell-Cell communication (Consensus)

Intolerance Scores

loftool: 0.151
rvis_EVS: -1.39
rvis_percentile_EVS: 4.27

Haploinsufficiency Scores

pHI: 0.106
hipred: Y
hipred_score: 0.662
ghis: 0.588

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: N
gene_indispensability_score: 0.211

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Kirrel3
Phenotype: craniofacial phenotype; growth/size/body region 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype;

Gene ontology

Biological process: neuron migration;inter-male aggressive behavior;homophilic cell adhesion via plasma membrane adhesion molecules;synapse assembly;principal sensory nucleus of trigeminal nerve development;hippocampus development;hemopoiesis;neuron projection morphogenesis;glomerulus morphogenesis
Cellular component: extracellular region;plasma membrane;integral component of membrane;axon;dendrite;dendritic shaft
Molecular function: protein binding