TAPT1

protein-coding

transmembrane anterior posterior transformation 1

Gene summary

This gene encodes a highly conserved protein that localizes to the centrosome and/or ciliary basal body. Mutations in this gene disrupt Golgi morphology and trafficking and normal primary cilium formation and these mutations are congenitally manifested by severe undermineralization of the intra-uterine skeleton. A mutation in the mouse ortholog of this gene results in homeotic, posterior-to-anterior transformations of the axial skeleton which are similar to the phenotype of mouse homeobox C8 gene mutants. In mouse, this gene is thought to function downstream of homeobox C8 to transduce extracellular patterning information during axial skeleton development. [provided by RefSeq, Jan 2017]

MANE transcript

NM_153365.3

Inheritance

ClinVar variants

P:10U:97B:81

Top phenotype

complex lethal osteochondrodysplasia

gnomAD constraint

pLI —, LoF o/e 0.3

Max pathogenic AF

—

Genomic locus

chr4:16,160,505-16,227,410

External References & Databases

Ensembl (ENSG00000169762)

Transcript & Mutation Effects

hg38 • Region Span ~66.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

complex lethal osteochondrodysplasiaSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014821

Submitter: G2P

complex lethal osteochondrodysplasiaSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014821

Submitter: Labcorp Genetics (formerly Invitae)

complex lethal osteochondrodysplasiaMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0014821

Submitter: PanelApp Australia

complex lethal osteochondrodysplasiaSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0014821

Submitter: Orphanet

cataractLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0005129

Submitter: G2P

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TAPT1 variants in ClinVar

10 Conditions Cataloged

not providedTotal: 232

Inborn genetic diseasesTotal: 56

not specifiedTotal: 15

TAPT1-related disorderTotal: 12

Complex lethal osteochondrodysplasiaTotal: 11

Reduced bone mineral densityTotal: 1

Short statureTotal: 1

ScoliosisTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_153365.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	71 clinvar	2 clinvar	74
missense	1 clinvar		93 clinvar	7 clinvar	1 clinvar	102
nonsense		2 clinvar				2
start loss			1 clinvar			1
frameshift	1 clinvar	1 clinvar				2
splice donor/acceptor (+/-2bp)	2 clinvar	3 clinvar	2 clinvar			7
Total	4	6	97	78	3	188

Highest pathogenic variant AF is 0.0000036936678

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 44 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_153365.3	RefSeq	NP_699196.2	14	MANE Select
ENST00000405303.7	Ensembl	ENSP00000385347.2	14	MANE Select
ENST00000505603.5	Ensembl	ENSP00000422652.1	3	Standard
ENST00000513782.1	Ensembl	ENSP00000423359.1	8	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
tapt1b	Danio rerio	Structure: cranial neural crest cell Quality: decreased amount abnormal

Gene / Model

Organism

Observed Phenotype

tapt1b

Danio rerio

Structure: cranial neural crest cell

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

ossification
in utero embryonic development
G protein-coupled receptor signaling pathway
post-embryonic development
neural crest cell development

Molecular Function

growth hormone-releasing hormone receptor activity

Cellular Component

endoplasmic reticulum
centrosome
integral component of membrane
integral component of endoplasmic reticulum membrane
ciliary basal body

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000405303
Coding exons: 14
Length: 66906
Individuals with no LoFs: 124627
Homozygous LoFs: 0
Heterozygous LoFs: 8
Defined: 124635
p: 0.0000321

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.92	157	241	0.652	0.0000117	3679
Missense (PolyPhen)		49	111.07	0.44116		1560
Synonymous	0.586	77	83.8	0.919	0.00000417	1059
Loss of Function	3.13	7	23.3	0.300	0.00000111	365

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000090	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000028	0.000027	rare
South Asian	0.000066	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Plays a role in primary cilia formation (PubMed:26365339). May act as a downstream effector of HOXC8 possibly by transducing or transmitting extracellular information required for axial skeletal patterning during development (By similarity). May be involved in cartilage and bone development (By similarity). May play a role in the differentiation of cranial neural crest cells (By similarity). {ECO:0000250|UniProtKB:A2BIE7, ECO:0000250|UniProtKB:Q4VBD2, ECO:0000269|PubMed:26365339}.;
Disease: DISEASE: Osteochondrodysplasia, complex lethal, Symoens-Barnes- Gistelinck type (OCLSBG) [MIM:616897]: An autosomal recessive, lethal syndrome characterized by severe hypomineralization of the entire skeleton, severe osteopenia, microcephaly, multiple intra- uterine fractures, and multiple congenital developmental anomalies affecting the brain, lungs, and kidneys. {ECO:0000269|PubMed:26365339}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.102

Intolerance Scores

RVIS EVS: 0.31
RVIS percentile EVS: 72.38

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.368

Gene Damage Prediction

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