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): 11:126423357-127003460

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 provided (43 variants)
• not specified (27 variants)
• Inborn genetic diseases (25 variants)
• Intellectual disability, autosomal dominant 4 (5 variants)
• KIRREL3-related condition (2 variants)
• Intellectual disability (1 variants)
• Difficulty walking;Thoracic scoliosis;Global developmental delay;Absent speech (1 variants)
• Developmental disorder (1 variants)
• Autism spectrum 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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			4	22	8	34
missense		2	35	7	2	46
nonsense				1		1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)		1				1
splice region			2		1	3
non coding					2	2
Total	0	3	39	30	12

Variants in KIRREL3

This is a list of pathogenic ClinVar variants found in the KIRREL3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
11-126424569-G-A			Benign (Jan 22, 2019)
11-126424615-G-A		Developmental disorder	Likely benign (Oct 21, 2021)
11-126424637-C-T			Likely benign (Jul 29, 2018)
11-126424688-G-A		not specified	Likely benign (Oct 23, 2019)
11-126424715-G-A		KIRREL3-related disorder	Likely benign (Dec 16, 2019)
11-126424726-C-A		Intellectual disability, autosomal dominant 4	Uncertain significance (Jul 25, 2018)
11-126424726-C-T			Uncertain significance (Nov 19, 2015)
11-126424743-G-A		not specified	Uncertain significance (Sep 20, 2023)
11-126424766-G-A		not specified	Benign (Dec 31, 2019)
11-126424799-A-C		KIRREL3-related disorder	Benign/Likely benign (Feb 07, 2020)
11-126424805-G-A		not specified	Likely benign (Sep 03, 2019)
11-126424843-C-T		not specified	Uncertain significance (Apr 25, 2022)
11-126424844-G-A		KIRREL3-related disorder	Likely benign (May 21, 2019)
11-126424857-C-T		not specified	Uncertain significance (Jan 23, 2023)
11-126424898-C-T		Intellectual disability, autosomal dominant 4	Likely pathogenic (Nov 19, 2015)
11-126424922-G-A		not specified	Benign (Jan 22, 2019)
11-126424926-G-A		not specified	Uncertain significance (May 14, 2014)
11-126424930-G-C		not specified	Uncertain significance (May 18, 2023)
11-126424932-C-T		Autism spectrum disorder	association (-)
11-126424934-C-T		not specified	Benign/Likely benign (Feb 01, 2023)
11-126424940-G-A		KIRREL3-related disorder	Likely benign (Mar 14, 2019)
11-126424950-C-T		not specified	Uncertain significance (May 04, 2023)
11-126424965-G-A		Intellectual disability	Uncertain significance (Jan 15, 2020)
11-126424978-G-A		not specified	Uncertain significance (Nov 29, 2023)
11-126424991-G-A		not specified	Likely benign (Oct 23, 2019)

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