TRPS1

transcriptional repressor GATA binding 1, the group of Zinc fingers C2H2-type|GATA zinc finger domain containing

Basic information

Region (hg38): 8:115408495-115809673

Links

ENSG00000104447 ∙ NCBI:7227 ∙ OMIM:604386 ∙ HGNC:12340 ∙ Uniprot:Q9UHF7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• trichorhinophalangeal syndrome type I (Definitive), mode of inheritance: AD
• trichorhinophalangeal syndrome type I or III (Supportive), mode of inheritance: AD
• trichorhinophalangeal syndrome, type III (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Trichorhinophalangeal syndrome, type I; Trichorhinophalangeal syndrome, type III	AD	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; Musculoskeletal; Neurologic	5991804; 10615131; 11112658; 19419465; 19610100; 19758263; 20394624; 21740822; 22481165 ; 27133561

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TRPS1 gene.

• Trichorhinophalangeal syndrome, type III;Trichorhinophalangeal dysplasia type I (201 variants)
• not provided (100 variants)
• Trichorhinophalangeal dysplasia type I;Trichorhinophalangeal syndrome, type III (86 variants)
• Trichorhinophalangeal dysplasia type I (57 variants)
• Inborn genetic diseases (47 variants)
• Trichorhinophalangeal syndrome (22 variants)
• not specified (11 variants)
• Trichorhinophalangeal syndrome, type III (7 variants)
• TRPS1-related condition (3 variants)
• Langer-Giedion syndrome (2 variants)
• Trichorhinophalangeal syndrome type I or III (2 variants)
• Proportionate short stature;Brachydactyly;Alopecia areata;Pear-shaped nose (1 variants)
• TRPS1-related disorder (1 variants)
• See cases (1 variants)
• Congenital anomaly of kidney and urinary tract (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TRPS1 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	68	13	83
missense	5	9	146	32	6	198
nonsense	30	4				34
start loss						0
frameshift	44	7	1			52
inframe indel			2			2
splice donor/acceptor (+/-2bp)	3	3				6
splice region			3	2		5
non coding			17	12	21	50
Total	82	23	168	112	40

Highest pathogenic variant AF is 0.00000658

Variants in TRPS1

This is a list of pathogenic ClinVar variants found in the TRPS1 region.

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

Position	Type	Phenotype	Significance	ClinVar
8-115408719-ATTCT-A		Trichorhinophalangeal syndrome	Likely benign (Jun 14, 2016)
8-115409172-ATAT-A		Trichorhinophalangeal syndrome	Uncertain significance (Jun 14, 2016)
8-115409261-G-GAAAAAAAA		Trichorhinophalangeal syndrome	Uncertain significance (Jun 14, 2016)
8-115409269-A-AAAAAAAAC			Likely benign (Jan 01, 2023)
8-115409281-AC-A		Trichorhinophalangeal syndrome	Uncertain significance (Jun 14, 2016)
8-115409420-CCCTTT-C		Trichorhinophalangeal syndrome	Uncertain significance (Jun 14, 2016)
8-115410484-TA-T		Trichorhinophalangeal syndrome	Uncertain significance (Jun 14, 2016)
8-115411268-CTAT-C		Trichorhinophalangeal syndrome	Uncertain significance (Jun 14, 2016)
8-115411282-GA-G		Trichorhinophalangeal syndrome	Uncertain significance (Jun 14, 2016)
8-115411485-GA-G		Trichorhinophalangeal syndrome	Likely benign (Jun 14, 2016)
8-115412039-A-AC		Trichorhinophalangeal syndrome	Uncertain significance (Jun 14, 2016)
8-115412179-TA-T		Trichorhinophalangeal syndrome	Uncertain significance (Jun 14, 2016)
8-115413684-AG-A		Trichorhinophalangeal syndrome	Uncertain significance (Jun 14, 2016)
8-115414041-A-AT		Trichorhinophalangeal syndrome, type III;Trichorhinophalangeal dysplasia type I	Uncertain significance (May 12, 2022)
8-115414053-T-G		Trichorhinophalangeal syndrome, type III;Trichorhinophalangeal dysplasia type I	Uncertain significance (Nov 19, 2023)
8-115414056-T-C		Trichorhinophalangeal dysplasia type I;Trichorhinophalangeal syndrome, type III	Likely benign (Oct 29, 2023)
8-115414060-T-C		Inborn genetic diseases	Uncertain significance (Jul 17, 2023)
8-115414062-G-T		Trichorhinophalangeal dysplasia type I;Trichorhinophalangeal syndrome, type III	Uncertain significance (Jul 18, 2022)
8-115414075-C-G		Trichorhinophalangeal dysplasia type I;Trichorhinophalangeal syndrome, type III	Uncertain significance (May 23, 2023)
8-115414110-C-T		Trichorhinophalangeal dysplasia type I;Trichorhinophalangeal syndrome, type III	Likely benign (Oct 06, 2023)
8-115414111-G-A		Trichorhinophalangeal dysplasia type I;Trichorhinophalangeal syndrome, type III • Inborn genetic diseases	Conflicting classifications of pathogenicity (Nov 28, 2023)
8-115414124-G-A			Likely pathogenic (Mar 22, 2016)
8-115414138-T-C		Trichorhinophalangeal syndrome, type III;Trichorhinophalangeal dysplasia type I	Conflicting classifications of pathogenicity (Nov 13, 2023)
8-115414152-G-A		Trichorhinophalangeal dysplasia type I;Trichorhinophalangeal syndrome, type III	Likely benign (Jan 08, 2024)
8-115414157-C-T		Trichorhinophalangeal dysplasia type I;Trichorhinophalangeal syndrome, type III	Uncertain significance (Oct 22, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TRPS1	protein_coding	protein_coding	ENST00000395715	6	401176

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.00000102	124686	0	2	124688	0.00000802

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.54	562	675	0.833	0.0000373	8551
Missense in Polyphen		229	342.13	0.66934		4372
Synonymous	-0.601	283	270	1.05	0.0000169	2490
Loss of Function	5.92	1	42.9	0.0233	0.00000234	584

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000178	0.0000177
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transcriptional repressor. Binds specifically to GATA sequences and represses expression of GATA-regulated genes at selected sites and stages in vertebrate development. Regulates chondrocyte proliferation and differentiation. Executes multiple functions in proliferating chondrocytes, expanding the region of distal chondrocytes, activating proliferation in columnar cells and supporting the differentiation of columnar into hypertrophic chondrocytes. {ECO:0000269|PubMed:12885770, ECO:0000269|PubMed:17391059}.
• Disease: DISEASE: Tricho-rhino-phalangeal syndrome 1 (TRPS1) [MIM:190350]: Autosomal dominant disorder characterized by craniofacial and skeletal abnormalities. It is allelic with tricho-rhino-phalangeal type 3. Typical features include sparse scalp hair, a bulbous tip of the nose, protruding ears, a long flat philtrum and a thin upper vermilion border. Skeletal defects include cone-shaped epiphyses at the phalanges, hip malformations and short stature. {ECO:0000269|PubMed:14560312}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Tricho-rhino-phalangeal syndrome 2 (TRPS2) [MIM:150230]: A syndrome that combines the clinical features of tricho-rhino- phalangeal syndrome type 1 and multiple exostoses type 1. Affected individuals manifest multiple dysmorphic facial features including large, laterally protruding ears, a bulbous nose, an elongated upper lip, as well as sparse scalp hair, winged scapulae, multiple cartilaginous exostoses, redundant skin, and mental retardation. Note=The gene represented in this entry is involved in disease pathogenesis. A chromosomal aberration resulting in the loss of functional copies of TRPS1 and EXT1 has been found in TRPS2 patients.; DISEASE: Tricho-rhino-phalangeal syndrome 3 (TRPS3) [MIM:190351]: Autosomal dominant disorder characterized by craniofacial and skeletal abnormalities. It is allelic with tricho-rhino-phalangeal type 1. In TRPS3 a more severe brachydactyly and growth retardation are observed. {ECO:0000269|PubMed:11112658, ECO:0000269|PubMed:11807863}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.134

Intolerance Scores

• loftool: 0.0223
• rvis_EVS: -1.75
• rvis_percentile_EVS: 2.36

Haploinsufficiency Scores

• pHI: 0.668
• hipred: Y
• hipred_score: 0.696
• ghis: 0.533

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.257

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Trps1
• 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); respiratory system phenotype; skeleton phenotype; renal/urinary system phenotype; digestive/alimentary phenotype; craniofacial phenotype; growth/size/body region 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); homeostasis/metabolism phenotype

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;skeletal system development;transcription by RNA polymerase II;NLS-bearing protein import into nucleus;regulation of chondrocyte differentiation;protein heterooligomerization
• Cellular component: nuclear chromatin;nucleus;nucleoplasm;protein-containing complex
• Molecular function: RNA polymerase II regulatory region sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription repressor activity, RNA polymerase II-specific;DNA-binding transcription factor activity;protein binding;zinc ion binding;protein domain specific binding