SIPA1L3

signal induced proliferation associated 1 like 3, the group of PDZ domain containing

Basic information

Region (hg38): 19:37907207-38208369

Links

ENSG00000105738 ∙ NCBI:23094 ∙ OMIM:616655 ∙ HGNC:23801 ∙ Uniprot:O60292 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• total early-onset cataract (Supportive), mode of inheritance: AD
• cataract 45 (Limited), mode of inheritance: Semidominant
• cataract 45 (Limited), mode of inheritance: AR
• cataract 45 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cataract 45	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	Ophthalmologic	25804400

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SIPA1L3 gene.

• Cataract 45 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SIPA1L3 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			1	46	18	65
missense			171	19	17	207
nonsense						0
start loss						0
frameshift	1					1
inframe indel			3	1	1	5
splice donor/acceptor (+/-2bp)						0
splice region			2	4	1	7
non coding				22	37	59
Total	1	0	175	88	73

Variants in SIPA1L3

This is a list of pathogenic ClinVar variants found in the SIPA1L3 region.

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

Position	Type	Phenotype	Significance	ClinVar
19-38080969-CA-C			Benign (Oct 06, 2019)
19-38081088-A-G			Benign (Jun 29, 2018)
19-38081569-A-G		not specified	Uncertain significance (Feb 15, 2023)
19-38081599-G-A		not specified	Uncertain significance (Nov 27, 2023)
19-38081603-A-G			Uncertain significance (Jun 01, 2023)
19-38081623-G-A		not specified	Uncertain significance (Apr 26, 2023)
19-38081635-G-A		not specified	Uncertain significance (Jun 02, 2023)
19-38081640-C-T			Benign (May 26, 2023)
19-38081641-C-T			Uncertain significance (Aug 09, 2022)
19-38081645-C-G			Uncertain significance (Dec 23, 2021)
19-38081664-C-G			Likely benign (Jan 16, 2023)
19-38081693-A-C			Uncertain significance (Oct 29, 2023)
19-38081727-GGCCACC-G			Conflicting classifications of pathogenicity (Dec 01, 2023)
19-38081727-GGCCACCGCCACC-G			Likely benign (Jun 30, 2023)
19-38081727-G-GGCCACC			Benign (Jan 18, 2024)
19-38081733-C-G			Likely benign (May 15, 2022)
19-38081737-A-C		not specified	Uncertain significance (Sep 17, 2021)
19-38081761-C-A		not specified	Uncertain significance (Dec 03, 2021)
19-38081778-T-A			Likely benign (Dec 31, 2019)
19-38081781-C-A			Likely benign (Dec 17, 2022)
19-38081781-C-T		SIPA1L3-related disorder	Likely benign (Nov 01, 2023)
19-38081831-A-G		not specified	Uncertain significance (Jun 09, 2022)
19-38081834-G-A		not specified	Uncertain significance (Feb 10, 2023)
19-38081893-G-A		not specified	Uncertain significance (Aug 12, 2021)
19-38081906-C-A			Benign (Jan 18, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SIPA1L3	protein_coding	protein_coding	ENST00000222345	20	301145

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.00000366	125714	0	34	125748	0.000135

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.55	1018	1.17e+3	0.872	0.0000805	11499
Missense in Polyphen		296	410.29	0.72144		4033
Synonymous	-0.659	555	536	1.04	0.0000421	3721
Loss of Function	6.72	7	65.9	0.106	0.00000352	715

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000188	0.000180
Ashkenazi Jewish	0.000403	0.000397
East Asian	0.0000548	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000191	0.000176
Middle Eastern	0.0000548	0.0000544
South Asian	0.0000986	0.0000980
Other	0.000352	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays a critical role in epithelial cell morphogenesis, polarity, adhesion and cytoskeletal organization in the lens (PubMed:26231217). {ECO:0000269|PubMed:26231217}.
• Disease: DISEASE: Note=A chromosomal translocation involving SIPA1L3 is found in a patient with bilateral severe ocular abnormalities including congenital cataracts, corneal clouding, iridocorneal and lenticular adhesions and microphthalmia. Chromosomal translocation t(2;19)(q37.3;q13.1). In addition to translocation, missense variant has been found in patient with bilateral congenital cataracts (PubMed:26231217). {ECO:0000269|PubMed:26231217}.; DISEASE: Cataract 45 (CTRCT45) [MIM:616851]: An opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. In general, the more posteriorly located and dense an opacity, the greater the impact on visual function. {ECO:0000269|PubMed:25804400}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Rap1 signaling pathway - Homo sapiens (human) (Consensus)

Recessive Scores

• pRec: 0.110

Intolerance Scores

• loftool: 0.132
• rvis_EVS: -1.61
• rvis_percentile_EVS: 2.95

Haploinsufficiency Scores

• pHI: 0.489
• hipred: Y
• hipred_score: 0.563
• ghis: 0.616

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.930

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Sipa1l3
• Phenotype: vision/eye phenotype

Zebrafish Information Network

• Gene name: sipa1l3
• Affected structure: eye
• Phenotype tag: abnormal
• Phenotype quality: perforate

Gene ontology

• Biological process: eye development;hematopoietic progenitor cell differentiation;epithelial cell morphogenesis;cytoskeleton organization;positive regulation of GTPase activity;regulation of small GTPase mediated signal transduction;establishment of epithelial cell polarity
• Cellular component: stress fiber;extracellular space;apical plasma membrane;apical part of cell;tricellular tight junction
• Molecular function: GTPase activator activity