PLS1

plastin 1, the group of EF-hand domain containing

Basic information

Region (hg38): 3:142596393-142713664

Links

ENSG00000120756 ∙ NCBI:5357 ∙ OMIM:602734 ∙ HGNC:9090 ∙ Uniprot:Q14651 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hearing loss, autosomal dominant 76 (Strong), mode of inheritance: AD
• hearing loss, autosomal dominant 76 (Moderate), mode of inheritance: AD
• autosomal dominant nonsyndromic hearing loss (Supportive), mode of inheritance: AD
• hearing loss, autosomal dominant 76 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal dominant 76	AD	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic	30872814; 31397523

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PLS1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PLS1 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				2	2	4
missense		1	56	3	3	63
nonsense						0
start loss						0
frameshift			1			1
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region			1		1	2
non coding					22	22
Total	0	1	58	5	27

Variants in PLS1

This is a list of pathogenic ClinVar variants found in the PLS1 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-142664153-A-T			Benign (May 26, 2021)
3-142664251-C-G		Inborn genetic diseases	Uncertain significance (Jul 14, 2024)
3-142664259-A-G		Inborn genetic diseases	Uncertain significance (Apr 20, 2024)
3-142664448-G-T			Benign (May 15, 2021)
3-142664476-G-A			Benign (May 15, 2021)
3-142669392-A-C		not specified	Uncertain significance (Feb 08, 2024)
3-142669455-C-T			Uncertain significance (Apr 19, 2022)
3-142669465-G-A		Inborn genetic diseases	Uncertain significance (Nov 20, 2024)
3-142669476-C-G		Inborn genetic diseases	Uncertain significance (Oct 16, 2023)
3-142669506-G-A		PLS1-related disorder	Likely benign (Aug 10, 2023)
3-142669512-A-G			Uncertain significance (Apr 12, 2024)
3-142669676-TGA-T			Benign (May 26, 2021)
3-142670783-A-G			Benign (May 24, 2021)
3-142670827-G-T			Benign (May 15, 2021)
3-142671014-A-G		Inborn genetic diseases	Uncertain significance (Jan 23, 2025)
3-142671036-G-A		Inborn genetic diseases	Uncertain significance (Aug 30, 2021)
3-142671056-G-A		Inborn genetic diseases	Uncertain significance (Aug 07, 2024)
3-142671067-T-G			Benign (May 06, 2021)
3-142671086-A-G		Inborn genetic diseases	Uncertain significance (May 22, 2023)
3-142671090-T-C		Inborn genetic diseases	Uncertain significance (Jan 26, 2025)
3-142671103-C-T		PLS1-related disorder	Likely benign (Jun 03, 2024)
3-142671159-G-T			Benign (May 26, 2021)
3-142671296-C-A			Benign (May 22, 2021)
3-142676111-A-G			Benign (May 22, 2021)
3-142676175-T-C		Hearing loss, autosomal dominant 76 • Autosomal dominant nonsyndromic hearing loss;Bilateral sensorineural hearing impairment	Likely pathogenic (Oct 16, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PLS1	protein_coding	protein_coding	ENST00000337777	15	117278

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000113	1.00	125679	0	68	125747	0.000270

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.48	252	327	0.770	0.0000161	4160
Missense in Polyphen		77	111.82	0.68861		1451
Synonymous	1.16	104	120	0.866	0.00000605	1165
Loss of Function	3.05	14	32.8	0.426	0.00000171	412

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000201	0.000185
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000522	0.000519
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.000653	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Actin-bundling protein in the absence of calcium.

Recessive Scores

• pRec: 0.163

Intolerance Scores

• loftool: 0.0938
• rvis_EVS: -0.4
• rvis_percentile_EVS: 26.93

Haploinsufficiency Scores

• pHI: 0.710
• hipred: Y
• hipred_score: 0.690
• ghis: 0.449

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.786

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pls1
• 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); hearing/vestibular/ear phenotype; digestive/alimentary phenotype; immune 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); cellular phenotype

Gene ontology

• Biological process: intestinal D-glucose absorption;regulation of microvillus length;positive regulation of multicellular organism growth;actin filament bundle assembly;actin filament network formation;terminal web assembly;positive regulation of protein localization to plasma membrane
• Cellular component: cytoplasm;actin filament;brush border;actin filament bundle;extracellular exosome;terminal web
• Molecular function: structural constituent of cytoskeleton;calcium ion binding;actin filament binding