TUFT1

protein-coding

tuftelin 1, the group of MicroRNA protein coding host genes

Gene summary

Tuftelin is an acidic protein that is thought to play a role in dental enamel mineralization and is implicated in caries susceptibility. It is also thought to be involved with adaptation to hypoxia, mesenchymal stem cell function, and neurotrophin nerve growth factor mediated neuronal differentiation. [provided by RefSeq, Aug 2014]

MANE transcript

NM_020127.3

Inheritance

ClinVar variants

P:2U:55B:6

Top phenotype

Woolly hair-skin fragility syndrome

gnomAD constraint

pLI —, LoF o/e 0.43

Max pathogenic AF

—

Genomic locus

chr1:151,540,305-151,583,583

External References & Databases

Ensembl (ENSG00000143367)

Transcript & Mutation Effects

hg38 • Region Span ~43.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

woolly hair-skin fragility syndromeMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0957307

Submitter: PanelApp Australia

woolly hair-skin fragility syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0957307

Submitter: Labcorp Genetics (formerly Invitae)

woolly hair-skin fragility syndromeMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0957307

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Woolly hair-skin fragility syndromeAR

Manifestation: Dermatologic

Intervention: General

Rationale: 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

Refs: 36689522

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TUFT1 variants in ClinVar

3 Conditions Cataloged

Inborn genetic diseasesTotal: 56

not providedTotal: 3

Woolly hair-skin fragility syndromeTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_020127.3. 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			1
missense			52 clinvar	5 clinvar	1 clinvar	58
nonsense						0
start loss						0
frameshift	1 clinvar		1 clinvar			2
splice donor/acceptor (+/-2bp)	1 clinvar		1 clinvar			2
Total	2	0	55	5	1	63

Highest pathogenic variant AF is 0.00002540301

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 29 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_020127.3	RefSeq	NP_064512.1	13	MANE Select
ENST00000368849.8	Ensembl	ENSP00000357842.3	13	MANE Select
NM_001126337.2	RefSeq	NP_001119809.1	12	Standard
NM_001301317.2	RefSeq	NP_001288246.1	13	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

bone mineralization
intracellular signal transduction
odontogenesis

Molecular Function

protein binding
structural constituent of tooth enamel

Cellular Component

extracellular region
cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000368849
Coding exons: 13
Length: 43279
Individuals with no LoFs: 125728
Homozygous LoFs: 0
Heterozygous LoFs: 19
Defined: 125747
p: 0.0000756

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.897	186	224	0.831	0.0000122	2558
Missense (PolyPhen)		48	66.11	0.72606		857
Synonymous	1.04	69	80.9	0.853	0.00000421	696
Loss of Function	2.67	11	25.6	0.430	0.00000125	291

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00016	0.00016	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000053	0.000053	rare
South Asian	0.00013	0.00013	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in the mineralization and structural organization of enamel. {ECO:0000250|UniProtKB:P27628}.;

Recessive Scores

pRec: 0.171

Intolerance Scores

LoFtool: 0.668
RVIS EVS: 0.37
RVIS percentile EVS: 75.43

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.621

Gene Damage Prediction

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