Pituitary hormone deficiency
Gene: ZRSR2EnsemblGeneIds (GRCh38): ENSG00000169249
EnsemblGeneIds (GRCh37): ENSG00000169249
OMIM: 300028, Gene2Phenotype
ZRSR2 is in 6 panels
1 review
Ida Ertmanska (Genomics England Curator)
Comment on list classification: There are 6 male individuals from 6 unrelated families reported in literature with hemizygous ZRSR2 variants and pituitary anomalies. Five individuals were shown to have deficiency of at least 2 pituitary hormones. Brain MRI showed absent or hypoplastic anterior pituitary gland and pituitary stalk in 5 cases. Based on available evidence, this gene can be promoted to Green on Pituitary hormone deficiency.Created: 6 Nov 2026, 2:41 p.m. | Last Modified: 6 Nov 2026, 2:41 p.m.
Panel Version: 4.16
PMID: 38158857 Hannes et al., 2024
Report of 8 boys from 6 unrelated families with Orofaciodigital syndrome from Argentina, Belgium, France, and Spain, including the family (family 4) originally described by PMID: 11003938 (Buño et al., 2000). One individual had holoprosencephaly with no further clinical details availalble. Overlapping phenotype: postaxial polydactyly (7/7), bilateral hallux duplication (5/7), brachydactyly (2/7), clinodactyly (2/7), high narrow palate (5/7), cleft palate (2/7), incisor anomalies (3/5), pituitary anomalies (6/7), holoprosencephaly (2/7), micropenis (4/7), seizures (2/7), bilateral cryptorchidism (5/6), short stature (4/5). Development was normal or mildly delayed. All probands harboured hemizygous ZRSR2 variants: c.1211_1212de, p.(Gly404GlufsTer23) in family 1, and c.1207_1208del, p.(Arg403GlyfsTer24) in the other 5 families.
Functional: Primary fibroblasts containing the NM_005089.4:c.1207_1208del ZRSR2 variant had abnormally elongated cilia.
PMID: 31680349 Guo et al., 2020
Trio-WES in families with recurrent fetal malformations.
Family 28 - 5 affected male fetuses, hemizygous for a ZRSR2 variant c.1207_1208del, p.(Arg403GlyfsTer24) - maternally inherited. Abnormal prenatal findings: congenital hydrocephalus, median cleft lip and palate, abnormal heart morphology, holoprosencephaly.
ZRSR2 is associated with XLR Orofaciodigital syndrome XXI, OMIM:30113 in OMIM; the assocation is rated as Moderate in Gene2Phenotype (resources accessed 6th Nov 2026).
Sources: LiteratureCreated: 6 Nov 2026, 2:27 p.m.
Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes
Orofaciodigital syndrome XXI, OMIM:301132; orofaciodigital syndrome, MONDO:0015375
Publications
Details
- Mode of Inheritance
- X-LINKED: hemizygous mutation in males, biallelic mutations in females
- Sources
-
- Expert Review Amber
- Literature
- Phenotypes
-
- Orofaciodigital syndrome XXI, OMIM:301132
- orofaciodigital syndrome, MONDO:0015375
- Tags
- OMIM
- 300028
- Clinvar variants
- Variants in ZRSR2
- Penetrance
- None
- Publications
- Panels with this gene
History Filter Activity
Entity classified by Genomics England curator
Ida Ertmanska (Genomics England Curator)Gene: zrsr2 has been classified as Amber List (Moderate Evidence).
Entity classified by Genomics England curator
Ida Ertmanska (Genomics England Curator)Gene: zrsr2 has been classified as Amber List (Moderate Evidence).
Created, Added New Source, Added Tag, Set mode of inheritance, Set publications, Set Phenotypes
Ida Ertmanska (Genomics England Curator)gene: ZRSR2 was added gene: ZRSR2 was added to Pituitary hormone deficiency. Sources: Literature Q4_26_promote_green tags were added to gene: ZRSR2. Mode of inheritance for gene: ZRSR2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: ZRSR2 were set to 11003938; 31680349; 38158857 Phenotypes for gene: ZRSR2 were set to Orofaciodigital syndrome XXI, OMIM:301132; orofaciodigital syndrome, MONDO:0015375 Review for gene: ZRSR2 was set to GREEN