TPM4

Inheritance Pattern: AD

Disease ID:MONDO:0100487

Submitter: ClinGen

*TPM4* was first reported in relation to inherited thrombocytopenia in 2017 (Pleines et al, PMID: 28134622). TPM4 encodes tropomyosin alpha 4 chain. Tropomyosins are dimers of coiled‐coil proteins that provide stability to the actin filaments in which they bind, regulating access of other actin‐binding proteins. *TPM4*- related platelet disorder (Bleeding Disorder, Platelet Type, 25) is an autosomal dominant platelet disorder characterized by variable thrombocytopenia, increased platelet size, and mild platelet dysfunction. Evidence supporting this gene-disease curation includes case-level data and experimental data. Summary of Case Level Data (4 points): Four unique variants have been reported in humans; two nonsense variants and two missense variants. Variants in this gene have been reported in at least 5 probands in 3 publications (Plienes et al, PMID: 28134622; Stapley et al, PMID: 34758189; Marin-Quilez et al, PMID:35170221). Variants in this gene segregated with disease in an additional 8 family members. Summary of Experimental Data (3 points): This gene disease relationship is supported by an animal model (Pleines et al, PMID: 28134622), Biochemical Function (Stapley et al, PMID: 34758189) and expression studies (Pleines et al, PMID: 28134622). In summary, there is moderate evidence to support this gene-disease relationship. Although more evidence is needed to support a causal role, no convincing evidence has emerged that contradicts the gene-disease relationship. This gene-disease classification was originally approved by the ClinGen Hemostasis and Thrombosis (H/T) Gene Curation Expert Panel on February 3, 2022 and re-evaluated on May 1, 2024. No new scoreable genetic or experimental evidence has emerged since the original curation date and as a result, the classification did not change. The ClinGen H/T expert panel is aware of an additional, unpublished case in which an individual with isolated thrombocytopenia and no family history of platelet or bleeding disorders is noted. The variant, *TPM4* (NM_001145160.1) c.572_574del, p.G191del results in an in-frame deletion of a single amino acid (CA2576659843). At this time, this variant is not scored in this curation.

Inheritance Pattern: AD

Disease ID:MONDO:0957580

Submitter: PanelApp Australia

Inheritance Pattern: AD

Disease ID:MONDO:0015372

Submitter: Orphanet