COL4A5

• Haploinsufficiency score: 3
• Strength of Evidence (disclaimer): Sufficient evidence for dosage pathogenicity
• Haploinsufficiency Phenotype: ALPORT SYNDROME 1, X-LINKED; ATS1

Evidence for haploinsufficiency phenotype

PubMed ID	Description
	King et al (2006) sequenced the COL4A5 gene in 25 unrelated patients with clear Alport syndrome and identified 21 mutations including four gross deletions, three frameshifts, three splice site mutations, and one inframe deletion.

Haploinsufficiency phenotype comments:

About 85% of Alport syndrome is caused by mutations in the collagen gene, COL4A5.

The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.

• Triplosensitivity score: 0
• Strength of Evidence (disclaimer): No evidence for dosage pathogenicity

The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.