Differences in sex development

Gene: TACR3

Red List (low evidence)

Comment on list classification: As reviewed by Rabina Akhtar, there are numerous individuals reported in literature with biallelic TACR3 variants and disease features matching the hypogonadotropic hypogonadism spectrum (delayed / arrested puberty). 3/15 cases reported in PMID: 20332248 were noted to have a small phallus at birth - also diagnosed with IHH. TACR3 is already Green on the Hypogonadotropic hypogonadism (GMS) panel, which is a better fit for the reported cases. Based on available evidence, this gene can only be rated Red on Differences in sex development, as no patients were reported to have significant genital abnormalities at birth.

Created: 7 Apr 2026, 9:25 a.m. | Last Modified: 7 Apr 2026, 9:25 a.m.

Panel Version: 4.17

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Hypogonadotropic hypogonadism 11 with or without anosmia, OMIM:614840; hypogonadotropic hypogonadism 11 with or without anosmia, MONDO:0013913

Publications

• 40101754
• 22031817
• 20332248

Green List (high evidence)

PMID:22031817 reports a 19 year old patient with small testes, micropenis and bilateral cryptorchidism, compound heterozygous TACR3 variant (c.824G>A and c.1003C>T)

PMID: 20332248 reports proband 3 of the study with micropenis and was found to be homozygous for TACR3 c.824G>A p.Trp275* variant

PMID: 40101754 performed a systematic review of the literature (245 publications) to extract clinical data and the association with gene variants from 775 males with delayed or arrested puberty due to CHH. The characteristics of the genitalia in patients with causal variants in the TACR3 was summarized in this paper. A total of 17 disease causing TACR3 variants were identified. Of those, 3 patients had cryptorchidism, 10 patients had micropenis, 2 patients had microorchidism, 3 patients had cryptorchidism and micropenis, and 2 patients had micropenis and microorchidism.

Additional male patient identified at WMGL with cryptorchidism and micropenis with a homozygous likely pathogenic TACR3 c.1057C>T p.(Pro353Ser)
Sources: Research, Literature

Created: 4 Feb 2026, 2:09 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
HYPOGONADOTROPIC HYPOGONADISM 11 WITH OR WITHOUT ANOSMIA; HH11 (OMIM: 614840)

Publications

• PMID: 22031817
• 20332248
• 40101754

Variants in this GENE are reported as part of current diagnostic practice