Pituitary hormone deficiency

Gene: BTK

Red List (low evidence)

Comment on list classification: There has been no experimental evidence and no further cases reported in literature linking BTK to Pituitary hormone deficiency since 1994. The association has been disputed by the ClinGen Antibody Deficiencies GCEP. Thus, this gene should be demoted to Red on the Pituitary hormone deficiency panel at the next GMS update.

Created: 29 Oct 2025, 4:39 p.m. | Last Modified: 29 Oct 2025, 4:39 p.m.

Panel Version: 4.1

The association between BTK and 'isolated growth hormone deficiency type III' has been classified as Disputed by ClinGen: 'No experimental evidence supporting a relationship with the isolated growth hormone deficiency has been reported and no convincing genetic evidence has emerged relating BTK to the isolated growth hormone deficiency since it was last reported in 1994. The evidence supporting the originally asserted relationship between BTK and x-linked isolated growth hormone deficiency type III has been disputed and no valid evidence remains to support the claim.' - Antibody Deficiencies GCEP, Nov 2020. More information can be found here: https://search.clinicalgenome.org/CCID:004296.
The gene was linked to Bruton-type agammaglobulinemia with a Definitive classification in a separate curation (https://search.clinicalgenome.org/CCID:004297)
BTK is linked to Isolated growth hormone deficiency, type III, with agammaglobulinemia, 307200 and Agammaglobulinemia, X-linked 1, 300755 in OMIM (accessed 29th Oct 2025).

Created: 29 Oct 2025, 4:39 p.m. | Last Modified: 29 Oct 2025, 4:39 p.m.

Panel Version: 4.1

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Phenotypes
Isolated growth hormone deficiency, type III, with agammaglobulinemia, OMIM:307200

Publications

• 7849697
• 8013627
• 1880652

As discussed in the GMS Endocrinology Specialist Test Group webex call 28th Jan 2019: The Specialist Test Group agreed that there is enough evidence to rate this gene green.

Created: 29 Jan 2019, noon

Comment on publications: BTK is confirmed to be associated with isolated growth hormone deficiency in OMIM but not in Gene2Phenotype. There are >3 unrelated cases of patients diagnosed with growth hormone deficiency who have variants in BTK.

Created: 10 Dec 2018, 12:25 p.m.