TSPEAR

thrombospondin type laminin G domain and EAR repeats

Basic information

Region (hg38): 21:44497893-44711572

Previous symbols: [ "C21orf29", "DFNB98" ]

Links

ENSG00000175894

∙ NCBI:54084 ∙ OMIM:612920 ∙ HGNC:1268 ∙ Uniprot:Q8WU66 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

autosomal recessive nonsyndromic hearing loss 98 (Disputed Evidence), mode of inheritance: AR
hearing loss, autosomal recessive (Supportive), mode of inheritance: AR
autosomal recessive nonsyndromic hearing loss 98 (Limited), mode of inheritance: AR
ectodermal dysplasia 14, hair/tooth type with or without hypohidrosis (Moderate), mode of inheritance: AR
autosomal recessive nonsyndromic hearing loss 98 (Limited), mode of inheritance: AR
ectodermal dysplasia 14, hair/tooth type with or without hypohidrosis (Strong), mode of inheritance: AR
nonsyndromic genetic hearing loss (Disputed Evidence), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal recessive 98	AR	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic; Craniofacial; Dental; Dermatologic	22678063; 27736875; 30046887; 32112661; 34042254

ClinVar

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

not_specified (849 variants)
not_provided (481 variants)
Inborn_genetic_diseases (121 variants)
TSPEAR-related_disorder (40 variants)
Ectodermal_dysplasia_14,_hair/tooth_type_with_or_without_hypohidrosis (37 variants)
Autosomal_recessive_nonsyndromic_hearing_loss_98 (25 variants)
Tooth_agenesis,_selective,_10 (23 variants)
Ectodermal_dysplasia_14,_hair/tooth_type,_with_hypohidrosis (2 variants)
TSPEAR-related_disorder_of_tooth_and_hair_follicle_morphogenesis (2 variants)
Myoepithelial_tumor (1 variants)
Hearing_impairment (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TSPEAR gene is commonly pathogenic or not. These statistics are base on transcript: NM_000144991.3. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous		1 clinvar	5 clinvar	85 clinvar	9 clinvar	100
missense	3 clinvar	11 clinvar	204 clinvar	31 clinvar		249
nonsense	16 clinvar	5 clinvar	3 clinvar			24
start loss	1					1
frameshift	21 clinvar	10 clinvar	1 clinvar			32
splice donor/acceptor (+/-2bp)	5 clinvar	4 clinvar	1 clinvar			10
Total	46	31	214	116	9

Highest pathogenic variant AF is 0.000565193

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TSPEAR	protein_coding	protein_coding	ENST00000323084	12	213721

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.44e-17	0.0298	125390	1	357	125748	0.00142

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.952	473	418	1.13	0.0000274	4307
Missense in Polyphen		128	103.24	1.2399		1186
Synonymous	-0.540	201	191	1.05	0.0000143	1396
Loss of Function	0.675	28	32.1	0.872	0.00000177	318

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00158	0.00155
Ashkenazi Jewish	0.000202	0.000198
East Asian	0.000875	0.000870
Finnish	0.000373	0.000370
European (Non-Finnish)	0.00232	0.00224
Middle Eastern	0.000875	0.000870
South Asian	0.00109	0.00105
Other	0.000985	0.000978

dbNSFP

Source: dbNSFP

Function: FUNCTION: May play a role in development or function of the auditory system.;
Disease: DISEASE: Deafness, autosomal recessive, 98 (DFNB98) [MIM:614861]: A form of non-syndromic sensorineural hearing loss with prelingual onset. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. {ECO:0000269|PubMed:22678063}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.128

Intolerance Scores

loftool
rvis_EVS: -1.08
rvis_percentile_EVS: 7.32

Haploinsufficiency Scores

pHI: 0.131
hipred: N
hipred_score: 0.264
ghis: 0.510

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: N
gene_indispensability_score: 0.114

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Tspear
Phenotype

Gene ontology

Biological process: sensory perception of sound
Cellular component: extracellular region;cell surface;stereocilium;ciliary membrane
Molecular function: molecular_function