PITX2

Chr 4AD

paired like homeodomain 2

Also known as: ARP1, ASGD4, Brx1, IDG2, IGDS, IGDS2, IHG2, IRID2

This gene encodes a member of the RIEG/PITX homeobox family, which is in the bicoid class of homeodomain proteins. The encoded protein acts as a transcription factor and regulates procollagen lysyl hydroxylase gene expression. This protein plays a role in the terminal differentiation of somatotroph and lactotroph cell phenotypes, is involved in the development of the eye, tooth and abdominal organs, and acts as a transcriptional regulator involved in basal and hormone-regulated activity of prolactin. Mutations in this gene are associated with Axenfeld-Rieger syndrome, iridogoniodysgenesis syndrome, and sporadic cases of Peters anomaly. A similar protein in other vertebrates is involved in the determination of left-right asymmetry during development. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Jul 2008]

GeneReviewsOMIMResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Anterior segment dysgenesis 4MIM #137600
AD
Axenfeld-Rieger syndrome, type 1MIM #180500
AD
Ring dermoid of corneaMIM #180550
AD

Clinical highlights

Gene-disease validity (ClinGen)
anterior segment dysgenesis 4 · ADDefinitivesufficient evidence for diagnostic panels
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.
0
Active trials
98
Pubs (1 yr)
P/LP submissions
P/LP missense
0.26
LOEUF· LoF intol.
LOF
Mechanism· G2P
📖
GeneReview available — PITX2
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint?
0.26LOEUF
pLI 0.976
Z-score 3.14
OE 0.00 (0.000.26)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?
1.55Z-score
OE missense 0.68 (0.580.79)
124 obs / 183.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.00 (0.000.26)
00.351.4
Missense OE?0.68 (0.580.79)
00.61.4
Synonymous OE?1.10
01.21.6
LoF obs/exp: 0 / 11.5Missense obs/exp: 124 / 183.0Syn Z: -0.67

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

PITX2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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