TRPS1

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

Basic information

Region (hg38): 8:115408496-115809673

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_dysplasia_type_I (530 variants)
• Trichorhinophalangeal_syndrome,_type_III (474 variants)
• Inborn_genetic_diseases (154 variants)
• not_provided (120 variants)
• TRPS1-related_disorder (22 variants)
• not_specified (10 variants)
• Trichorhinophalangeal_syndrome (3 variants)
• Microcephaly (3 variants)
• Trichorhinophalangeal_syndrome_type_I_or_III (2 variants)
• Langer-Giedion_syndrome (2 variants)
• Craniosynostosis_syndrome (1 variants)
• Pear-shaped_nose (1 variants)
• Metaphyseal_chondrodysplasia (1 variants)
• Mitral_valve_prolapse (1 variants)
• Alopecia_areata (1 variants)
• Abnormally_high-pitched_voice (1 variants)
• Proportionate_short_stature (1 variants)
• Sparse_hair (1 variants)
• See_cases (1 variants)
• Sparse_and_thin_eyebrow (1 variants)
• Hyperextensible_skin (1 variants)
• Short_stature (1 variants)
• Congenital_anomaly_of_kidney_and_urinary_tract (1 variants)
• Brachydactyly (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. These statistics are base on transcript: NM_000014112.5. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	111	15	129
missense	7	14	308	67	8	404
nonsense	47	6	3			56
start loss						0
frameshift	66	15	13			94
splice donor/acceptor (+/-2bp)	3	6	1			10
Total	123	41	328	178	23

Highest pathogenic variant AF is 0.00000658389

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