TAT

Chr 16AR

tyrosine aminotransferase

NCBI Gene: 6898 ENSG00000198650 UniProt: P17735 OMIM: 613018

This gene encodes tyrosine aminotransferase, a mitochondrial enzyme that converts tyrosine to p-hydroxyphenylpyruvate in the liver as part of tyrosine catabolism. Biallelic mutations cause tyrosinemia type II (Richner-Hanhart syndrome), an autosomal recessive disorder characterized by painful palmoplantar keratoderma, corneal lesions, and variable intellectual disability. The gene is relatively tolerant to loss-of-function variants in the general population (pLI 0.007).

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This nuclear gene encodes a mitochondrial protein tyrosine aminotransferase which is present in the liver and catalyzes the conversion of L-tyrosine into p-hydroxyphenylpyruvate. Mutations in this gene cause tyrosinemia (type II, Richner-Hanhart syndrome), a disorder accompanied by major skin and corneal lesions, with possible cognitive disability. A regulator gene for tyrosine aminotransferase is X-linked. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Tyrosinemia, type IIMIM #276600

UniProtTyrosinemia 2

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · tyrosinemia type II · AR · ClinGen 2020

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

1307

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.61

LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — TAT

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.61LOEUF

pLI 0.007

Z-score 2.97

OE 0.34 (0.20–0.61)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.76Z-score

OE missense 0.87 (0.78–0.97)

220 obs / 254.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.34 (0.20–0.61)

0≤0.351.4

Missense OE?0.87 (0.78–0.97)

0≤0.61.4

Synonymous OE?0.95

0≤1.21.6

LoF obs/exp: 8 / 23.5Missense obs/exp: 220 / 254.1Syn Z: 0.38

Background carrier burden — how many people carry a rare variant somewhere in TAT?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 150

564 rare PASS variants

Rare truncating (LoF)

1 in 3,000

73 rare PASS variants

Rare synonymous (reference)

1 in 310

209 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TAT. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 170	1 in 3,500
South Asian	~43k	1 in 91	1 in 1,200
Remaining (unassigned)	~30k	1 in 150	1 in 3,800
European (Finnish)	~27k	1 in 930	≈ 1 in 13,000
Admixed American	~22k	1 in 120	≈ 1 in 4,500
African / African American	~21k	1 in 110	1 in 1,800
East Asian	~20k	1 in 130	1 in 3,700
Ashkenazi Jewish	~13k	1 in 770	none seen
Middle Eastern	~2,884	1 in 130	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.