RELN

reelin

Basic information

Region (hg38): 7:103471380-103989658

Links

ENSG00000189056 ∙ NCBI:5649 ∙ OMIM:600514 ∙ HGNC:9957 ∙ Uniprot:P78509 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Norman-Roberts syndrome (Definitive), mode of inheritance: AR
• Norman-Roberts syndrome (Definitive), mode of inheritance: AR
• Norman-Roberts syndrome (Strong), mode of inheritance: AR
• Norman-Roberts syndrome (Supportive), mode of inheritance: AR
• autosomal dominant epilepsy with auditory features (Supportive), mode of inheritance: AD
• familial temporal lobe epilepsy 7 (Moderate), mode of inheritance: AD
• Norman-Roberts syndrome (Moderate), mode of inheritance: AR
• ankylosing spondylitis (Limited), mode of inheritance: AD
• familial temporal lobe epilepsy 7 (Strong), mode of inheritance: AD
• Norman-Roberts syndrome (Strong), mode of inheritance: AR
• lissencephaly with cerebellar hypoplasia (Definitive), mode of inheritance: AR
• complex neurodevelopmental disorder (Disputed Evidence), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Epilepsy, familial temporal lobe, 7; Lissencephaly 2	AD/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	Craniofacial; Neurologic	10973257; 17431900; 26046367

ClinVar

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

• Norman-Roberts syndrome;Familial temporal lobe epilepsy 7 (1522 variants)
• not provided (793 variants)
• Familial temporal lobe epilepsy 7;Norman-Roberts syndrome (763 variants)
• Norman-Roberts syndrome (259 variants)
• not specified (212 variants)
• Inborn genetic diseases (135 variants)
• Familial temporal lobe epilepsy 7 (38 variants)
• Epilepsy, familial temporal lobe, 1;Norman-Roberts syndrome;Familial temporal lobe epilepsy 7 (21 variants)
• RELN-related condition (18 variants)
• Norman-Roberts syndrome;Epilepsy, familial temporal lobe, 1;Familial temporal lobe epilepsy 7 (18 variants)
• Lissencephaly, Recessive (17 variants)
• Epilepsy, familial temporal lobe, 1;Familial temporal lobe epilepsy 7;Norman-Roberts syndrome (12 variants)
• Norman-Roberts syndrome;Familial temporal lobe epilepsy 7;Epilepsy, familial temporal lobe, 1 (11 variants)
• Familial temporal lobe epilepsy 7;Norman-Roberts syndrome;Epilepsy, familial temporal lobe, 1 (10 variants)
• See cases (8 variants)
• Familial temporal lobe epilepsy 7;Epilepsy, familial temporal lobe, 1;Norman-Roberts syndrome (6 variants)
• Childhood epilepsy with centrotemporal spikes (6 variants)
• Intellectual disability (5 variants)
• Seizure (4 variants)
• - (2 variants)
• Autism (2 variants)
• Lissencephaly (2 variants)
• RELN-related disorder (1 variants)
• Neurodevelopmental delay (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RELN 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			39	472	32	543
missense		4	1130	131	19	1284
nonsense	14	4	1			19
start loss			2			2
frameshift	17	7	1			25
inframe indel			18			18
splice donor/acceptor (+/-2bp)	1	8	1			10
splice region			64	98	18	180
non coding			39	364	195	598
Total	32	23	1231	967	246

Highest pathogenic variant AF is 0.0000197

Variants in RELN

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

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

Position	Type	Phenotype	Significance	ClinVar
7-103471955-A-G		Norman-Roberts syndrome	Uncertain significance (Jan 13, 2018)
7-103472005-ACT-A		Lissencephaly, Recessive	Uncertain significance (Jun 14, 2016)
7-103472152-G-T		Lissencephaly, Recessive	Uncertain significance (Jun 14, 2016)
7-103472236-C-T		Norman-Roberts syndrome	Likely benign (Jan 13, 2018)
7-103472249-G-T		Norman-Roberts syndrome	Benign (Jan 13, 2018)
7-103472286-T-C		Norman-Roberts syndrome	Uncertain significance (Jan 13, 2018)
7-103472325-G-A		Norman-Roberts syndrome	Uncertain significance (Jan 12, 2018)
7-103472415-C-T		Norman-Roberts syndrome	Benign (Jan 12, 2018)
7-103472438-C-G		Norman-Roberts syndrome	Uncertain significance (Jan 13, 2018)
7-103472549-A-G		Norman-Roberts syndrome	Uncertain significance (Jan 13, 2018)
7-103472661-A-G		Norman-Roberts syndrome	Benign (Jun 26, 2018)
7-103472676-C-T		Norman-Roberts syndrome	Uncertain significance (Jan 12, 2018)
7-103472677-G-A		Norman-Roberts syndrome	Uncertain significance (Jan 13, 2018)
7-103472703-C-T		Norman-Roberts syndrome	Uncertain significance (Jan 12, 2018)
7-103472718-A-G		Norman-Roberts syndrome	Uncertain significance (Jan 13, 2018)
7-103472730-A-G		Norman-Roberts syndrome	Uncertain significance (Jan 13, 2018)
7-103472731-T-C		Norman-Roberts syndrome	Uncertain significance (Jan 13, 2018)
7-103472744-G-A		Norman-Roberts syndrome	Uncertain significance (Jan 13, 2018)
7-103472745-C-T		Norman-Roberts syndrome	Benign (Jul 27, 2018)
7-103472775-C-T		Norman-Roberts syndrome	Uncertain significance (Jan 12, 2018)
7-103472814-A-G		Norman-Roberts syndrome;Familial temporal lobe epilepsy 7	Uncertain significance (Sep 14, 2023)
7-103472822-C-T		Norman-Roberts syndrome;Familial temporal lobe epilepsy 7	Uncertain significance (Jul 10, 2023)
7-103472823-G-A		Norman-Roberts syndrome;Familial temporal lobe epilepsy 7	Uncertain significance (Jul 26, 2022)
7-103472827-A-G		Familial temporal lobe epilepsy 7;Norman-Roberts syndrome	Likely benign (Mar 19, 2022)
7-103472837-C-T		Norman-Roberts syndrome;Familial temporal lobe epilepsy 7 • Inborn genetic diseases	Uncertain significance (Dec 21, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RELN	protein_coding	protein_coding	ENST00000428762	65	517733

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	4.25e-14	125716	0	32	125748	0.000127

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.25	1577	1.85e+3	0.853	0.000103	22857
Missense in Polyphen		570	728.27	0.78268		8878
Synonymous	-1.09	716	680	1.05	0.0000409	6462
Loss of Function	11.0	23	185	0.124	0.00000954	2131

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000210	0.000210
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000218	0.000217
Finnish	0.00	0.00
European (Non-Finnish)	0.000187	0.000185
Middle Eastern	0.000218	0.000217
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Extracellular matrix serine protease that plays a role in layering of neurons in the cerebral cortex and cerebellum. Regulates microtubule function in neurons and neuronal migration. Affects migration of sympathetic preganglionic neurons in the spinal cord, where it seems to act as a barrier to neuronal migration. Enzymatic activity is important for the modulation of cell adhesion. Binding to the extracellular domains of lipoprotein receptors VLDLR and LRP8/APOER2 induces tyrosine phosphorylation of DAB1 and modulation of TAU phosphorylation (By similarity). {ECO:0000250}.
• Disease: DISEASE: Lissencephaly 2 (LIS2) [MIM:257320]: A classic type lissencephaly associated with ataxia, mental retardation, seizures and abnormalities of the cerebellum, hippocampus and brainstem. {ECO:0000269|PubMed:10973257}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Epilepsy, familial temporal lobe, 7 (ETL7) [MIM:616436]: A focal form of epilepsy characterized by recurrent seizures that arise from foci within the temporal lobe. Seizures are usually accompanied by sensory symptoms, most often auditory in nature. {ECO:0000269|PubMed:26046367}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: PI3K-Akt signaling pathway - Homo sapiens (human);ECM-receptor interaction - Homo sapiens (human);Focal adhesion - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);Focal Adhesion;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;PI3K-Akt Signaling Pathway;Developmental Biology;lissencephaly gene (lis1) in neuronal migration and development;Axon guidance;Reelin signalling pathway;Reelin signaling pathway;Lissencephaly gene (LIS1) in neuronal migration and development (Consensus)

Intolerance Scores

• loftool: 0.175
• rvis_EVS: -2.15
• rvis_percentile_EVS: 1.46

Haploinsufficiency Scores

• pHI: 0.251
• hipred: Y
• hipred_score: 0.782
• ghis: 0.562

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.897

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Reln
• Phenotype: reproductive system phenotype; 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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); digestive/alimentary phenotype; vision/eye phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; cellular phenotype; muscle phenotype

Gene ontology

• Biological process: cell morphogenesis involved in differentiation;neuron migration;proteolysis;cell adhesion;axon guidance;central nervous system development;brain development;long-term memory;associative learning;glial cell differentiation;positive regulation of neuron projection development;positive regulation of phosphatidylinositol 3-kinase signaling;dendrite development;peptidyl-tyrosine phosphorylation;spinal cord patterning;ventral spinal cord development;hippocampus development;cerebral cortex tangential migration;layer formation in cerebral cortex;positive regulation of TOR signaling;positive regulation of CREB transcription factor activity;reelin-mediated signaling pathway;positive regulation of protein kinase activity;response to pain;positive regulation of peptidyl-tyrosine phosphorylation;regulation of behavior;modulation of chemical synaptic transmission;positive regulation of small GTPase mediated signal transduction;positive regulation of synaptic transmission, glutamatergic;long-term synaptic potentiation;positive regulation of dendritic spine morphogenesis;positive regulation of protein tyrosine kinase activity;positive regulation of synapse maturation;NMDA glutamate receptor clustering;postsynaptic density protein 95 clustering;receptor localization to synapse;lateral motor column neuron migration;positive regulation of long-term synaptic potentiation;positive regulation of lateral motor column neuron migration;regulation of NMDA receptor activity;positive regulation of excitatory postsynaptic potential;positive regulation of AMPA receptor activity
• Cellular component: extracellular region;extracellular space;cytoplasm;plasma membrane;dendrite;extracellular matrix
• Molecular function: serine-type peptidase activity;metal ion binding;lipoprotein particle receptor binding;very-low-density lipoprotein particle receptor binding