KIRREL3 (kirre like nephrin family adhesion molecule 3)

Gene

• Entrez ID: 84623
• Gene name: Kirre like nephrin family adhesion molecule 3
• Gene symbol: KIRREL3
• Synonyms (NCBI Gene): KIRRE, MRD4, NEPH2, PRO4502
• Chromosome: 11
• Chromosome location: 11q24.2
• Summary: The protein encoded by this gene is a member of the nephrin-like protein family. These proteins are expressed in fetal and adult brain, and also in podocytes of kidney glomeruli. The cytoplasmic domains of these proteins interact with the C-terminus of po

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs1057519593	C>A,T	Likely-pathogenic	Coding sequence variant, genic downstream transcript variant, missense variant
rs1064795581	C>T	Likely-pathogenic	Splice donor variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT440363	hsa-miR-218-5p	HITS-CLIP	23212916
MIRT440363	hsa-miR-218-5p	HITS-CLIP	23212916
MIRT1095296	hsa-miR-1251	CLIP-seq
MIRT1095297	hsa-miR-1273f	CLIP-seq
MIRT1095298	hsa-miR-3613-5p	CLIP-seq
MIRT1095299	hsa-miR-3674	CLIP-seq
MIRT1095300	hsa-miR-4305	CLIP-seq
MIRT1095301	hsa-miR-4732-5p	CLIP-seq
MIRT1095302	hsa-miR-615-5p	CLIP-seq
MIRT1095303	hsa-miR-2467-3p	CLIP-seq
MIRT1095304	hsa-miR-3192	CLIP-seq
MIRT1095305	hsa-miR-3197	CLIP-seq
MIRT1095306	hsa-miR-3689a-3p	CLIP-seq
MIRT1095307	hsa-miR-3689c	CLIP-seq
MIRT1095308	hsa-miR-4728-5p	CLIP-seq
MIRT1095309	hsa-miR-485-5p	CLIP-seq
MIRT2025564	hsa-miR-3690	CLIP-seq
MIRT2025565	hsa-miR-377	CLIP-seq
MIRT2025566	hsa-miR-4290	CLIP-seq
MIRT2025567	hsa-miR-4459	CLIP-seq
MIRT2025568	hsa-miR-4690-3p	CLIP-seq
MIRT2025569	hsa-miR-4779	CLIP-seq
MIRT2025570	hsa-miR-548u	CLIP-seq
MIRT2025571	hsa-miR-665	CLIP-seq
MIRT2025572	hsa-miR-766	CLIP-seq
MIRT2256797	hsa-miR-2682	CLIP-seq
MIRT2256798	hsa-miR-34a	CLIP-seq
MIRT2256799	hsa-miR-34c-5p	CLIP-seq
MIRT2256800	hsa-miR-3714	CLIP-seq
MIRT2025566	hsa-miR-4290	CLIP-seq
MIRT2256801	hsa-miR-449a	CLIP-seq
MIRT2256802	hsa-miR-449b	CLIP-seq
MIRT2256803	hsa-miR-449c	CLIP-seq
MIRT2025572	hsa-miR-766	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001764	Process	Neuron migration	IEA
GO:0002121	Process	Inter-male aggressive behavior	IEA
GO:0005515	Function	Protein binding	IPI	12424224, 25902260, 34799561
GO:0005576	Component	Extracellular region	IEA
GO:0005576	Component	Extracellular region	ISS
GO:0005886	Component	Plasma membrane	IBA
GO:0005886	Component	Plasma membrane	IEA
GO:0005886	Component	Plasma membrane	TAS
GO:0005911	Component	Cell-cell junction	IBA
GO:0007156	Process	Homophilic cell adhesion via plasma membrane adhesion molecules	IEA
GO:0007156	Process	Homophilic cell adhesion via plasma membrane adhesion molecules	ISS
GO:0007416	Process	Synapse assembly	IBA
GO:0007416	Process	Synapse assembly	IEA
GO:0007416	Process	Synapse assembly	ISS
GO:0008021	Component	Synaptic vesicle	IDA	25902260
GO:0016020	Component	Membrane	IEA
GO:0016020	Component	Membrane	ISS
GO:0021740	Process	Principal sensory nucleus of trigeminal nerve development	IEA
GO:0021766	Process	Hippocampus development	IEA
GO:0021766	Process	Hippocampus development	ISS
GO:0030097	Process	Hemopoiesis	IEA
GO:0030097	Process	Hemopoiesis	ISS
GO:0030424	Component	Axon	IEA
GO:0030424	Component	Axon	ISS
GO:0030425	Component	Dendrite	IEA
GO:0030425	Component	Dendrite	ISS
GO:0043198	Component	Dendritic shaft	IEA
GO:0048812	Process	Neuron projection morphogenesis	IEA
GO:0050839	Function	Cell adhesion molecule binding	IBA
GO:0072102	Process	Glomerulus morphogenesis	IEA
GO:0098609	Process	Cell-cell adhesion	IBA

Other IDs

• MIM: 607761
• HGNC: 23204
• e!Ensembl: ENSG00000149571

Protein

• UniProt ID: Q8IZU9
• Protein name: Kin of IRRE-like protein 3 (Kin of irregular chiasm-like protein 3) (Nephrin-like protein 2) [Cleaved into: Processed kin of IRRE-like protein 3]
• Protein 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 c
• PDB: 2CRY
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF07679	I-set	48 → 145	Immunoglobulin I-set domain	Domain
  PF13895	Ig_2	149 → 246	Immunoglobulin domain	Domain
  PF07679	I-set	335 → 416	Immunoglobulin I-set domain	Domain
  PF13927	Ig_3	419 → 503		Domain

• Tissue specificity: TISSUE SPECIFICITY: Expressed in fetal and adult brain (PubMed:19012874). Also expressed in kidney, specifically in podocytes of kidney glomeruli (PubMed:12424224). Also expressed in skeletal muscle (PubMed:25488023). {ECO:0000269|PubMed:12424224, ECO:000
• Sequence:

  MKPFQLDLLFVCFFLFSQELGLQKRGCCLVLGYMAKDKFRRMNEGQVYSFSQQPQDQVVV
  SGQPVTLLCAIPEYDGFVLWIKDGLALGVGRDLSSYPQYLVVGNHLSGEHHLKILRAELQ
  DDAVYECQAIQAAIRSRPARLTVLVPPDDPVILGGPVISLRAGDPLNLTCHADNAKPAAS
  IIWLRKGEVINGATYSKTLLRDGKRESIVSTLFISPGDVENGQSIVCRATNKAIPGGKET
  SVTIDIQHPPLVNLSVEPQPVLEDNVVTFHCSAKANPAVTQYRWAKRGQIIKEASGEVYR
  TTVDYTYFSEPVSCEVTNALGSTNLSRTVDVYFGPRMTTEPQSLLVDLGSDAIFSCAWTG
  NPSLTIVWMKRGSGVVLSNEKTLTLKSVRQEDAGKYVCRAVVPRVGAGEREVTLTVNGPP
  IISSTQTQHALHGEKGQIKCFIRSTPPPDRIAWSWKENVLESGTSGRYTVETISTEEGVI
  STLTISNIVRADFQTIYNCTAWNSFGSDTEIIRLKEQGSEMKSGAGLEAESVPMAVIIGV
  AVGAGVAFLVLMATIVAFCCARSQRNLKGVVSAKNDIRVEIVHKEPASGREGEEHSTIKQ
  LMMDRGEFQQDSVLKQLEVLKEEEKEFQNLKDPTNGYYSVNTFKEHHSTPTISLSSCQPD
  LRPAGKQRVPTGMSFTNIYSTLSGQGRLYDYGQRFVLGMGSSSIELCEREFQRGSLSDSS
  SFLDTQCDSSVSSSGKQDGYVQFDKASKASASSSHHSQSSSQNSDPSRPLQRRMQTHV

• Sequence length: 778

Pathways

Reactome:

Nephrin family interactions

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Intellectual disability, autosomal dominant 4	Likely pathogenic	rs1057519593	RCV000417096	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Absent speech	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATTENTION DEFICIT HYPERACTIVITY DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Autism spectrum disorder	Uncertain significance; association	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTISM SPECTRUM DISORDERS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTOSOMAL DOMINANT NON-SYNDROMIC INTELLECTUAL DISABILITY	—	Disgenet, Orphanet Disgenet, Orphanet Disgenet, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CENTRAL NERVOUS SYSTEM CANCER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COLORECTAL CANCER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COMPLEX NEURODEVELOPMENTAL DISORDER	—	ClinGen	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONDUCT DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CORONARY ARTERY DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DEMENTIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Developmental disorder	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Difficulty walking	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GLIOBLASTOMA MULTIFORME	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GLIOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Global developmental delay	Uncertain significance	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Intellectual disability	Uncertain significance	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
KIRREL3-related disorder	Benign; Likely benign; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MAJOR DEPRESSIVE DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MENTAL RETARDATION, AUTOSOMAL DOMINANT 4	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NEUROTIC DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NON-SPECIFIC SYNDROMIC INTELLECTUAL DISABILITY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OLIGODENDROGLIOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCHIZOPHRENIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SPERMATOCELE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thoracic scoliosis	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
VENOUS THROMBOEMBOLISM	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Apraxias	Apraxia	Pubtator	37605258	Associate	★☆☆☆☆ Found in Text Mining only
Autism Spectrum Disorder	Autism	Pubtator	29271092, 37605258	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Autism Spectrum Disorders	Autism Spectrum Disorder	BEFREE	22965935, 25902260, 27743928, 28381988, 29271092, 29362445		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Autistic Disorder	Autism	Pubtator	22521361, 23575222	Associate	★☆☆☆☆ Found in Text Mining only
Autistic Disorder	Autism	BEFREE	30133126		★☆☆☆☆ Found in Text Mining only
Autosomal dominant non-syndromic intellectual disability	Non-Syndromic Intellectual Disability	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Carcinoma Hepatocellular	Hepatocellular carcinoma	Pubtator	30945699	Associate	★☆☆☆☆ Found in Text Mining only
Cerebellar Diseases	Cerebellar diseases	Pubtator	37605258	Associate	★☆☆☆☆ Found in Text Mining only
Cerebellar Hypoplasia	Cerebellar hypoplasia	Pubtator	37605258	Associate	★☆☆☆☆ Found in Text Mining only
Chronic Lymphocytic Leukemia	Lymphocytic Leukemia	BEFREE	31537528		★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	38092774	Associate	★☆☆☆☆ Found in Text Mining only
Congenital Abnormalities	Congenital abnormalities	Pubtator	37605258	Associate	★☆☆☆☆ Found in Text Mining only
Congenital anomaly of brain	Brain malformation	BEFREE	19012874		★☆☆☆☆ Found in Text Mining only
Congenital anomaly of face	Facial dysmorphism	BEFREE	29271092		★☆☆☆☆ Found in Text Mining only
Degenerative polyarthritis	Arthritis	GWASDB_DG	22763110		★☆☆☆☆ Found in Text Mining only
Facial Dysmorphism with Multiple Malformations	Facial dysmorphism syndrome	Pubtator	29271092	Associate	★☆☆☆☆ Found in Text Mining only
Gastrointestinal Stromal Tumors	Gastrointestinal stromal tumor	BEFREE	24133624		★☆☆☆☆ Found in Text Mining only
Gastrointestinal Stromal Tumors	Gastrointestinal stromal tumor	Pubtator	24133624	Associate	★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	BEFREE	19012874, 25902260, 29271092, 29362445		★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Intellectual Disability	Intellectual developmental disorder	Pubtator	19012874, 29271092, 37605258	Associate	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Jacobsen Distal 11q Deletion Syndrome	Jacobsen Syndrome	BEFREE	22965935, 25902260, 30133126		★☆☆☆☆ Found in Text Mining only
Mental Retardation, Autosomal Dominant 4	Mental retardation	GENOMICS_ENGLAND_DG	19012874		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Mental Retardation, Autosomal Dominant 4	Mental retardation	CLINVAR_DG	19012874		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Neurodevelopmental Disorders	Neurodevelopmental Disorders	BEFREE	29362445, 30133126		★☆☆☆☆ Found in Text Mining only
Pervasive Development Disorder	Autism spectrum disorder	BEFREE	22965935, 25902260		★☆☆☆☆ Found in Text Mining only
Severe intellectual disability	Mental retardation	BEFREE	19012874		★☆☆☆☆ Found in Text Mining only