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Ehlers Danlos syndrome with a likely monogenic cause v4.20 ATP6V1E1 Ida Ertmanska Tag Q3_26_promote_green tag was added to gene: ATP6V1E1.
Ehlers Danlos syndrome with a likely monogenic cause v4.20 ATP6V1E1 Ida Ertmanska Tag Q3_26_promote_green was removed from gene: ATP6V1E1.
Ehlers Danlos syndrome with a likely monogenic cause v4.20 ATP6V1E1 Ida Ertmanska Classified gene: ATP6V1E1 as Amber List (moderate evidence)
Ehlers Danlos syndrome with a likely monogenic cause v4.20 ATP6V1E1 Ida Ertmanska Added comment: Comment on list classification: There are 3 unrelated individuals reported in literature with biallelic ATP6V1E1 variants and syndromic cutis laxa, with variable features including congenital heart defects, hypotonia, aortic dilation, contractures, and more. Hence, this gene can be promoted to Green on Ehlers Danlos syndrome with a likely monogenic cause.
Ehlers Danlos syndrome with a likely monogenic cause v4.20 ATP6V1E1 Ida Ertmanska Gene: atp6v1e1 has been classified as Amber List (Moderate Evidence).
Ehlers Danlos syndrome with a likely monogenic cause v4.19 ATP6V1E1 Ida Ertmanska gene: ATP6V1E1 was added
gene: ATP6V1E1 was added to Ehlers Danlos syndrome with a likely monogenic cause. Sources: Literature
Q3_26_promote_green tags were added to gene: ATP6V1E1.
Mode of inheritance for gene: ATP6V1E1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATP6V1E1 were set to 27023906; 28065471
Phenotypes for gene: ATP6V1E1 were set to Cutis laxa, autosomal recessive, type IIC, OMIM:617402; autosomal recessive cutis laxa type 2C, MONDO:0027462
Review for gene: ATP6V1E1 was set to GREEN
Added comment: PMID: 27023906 Alazami et al., 2016
Study of a cohort of 40 families with inherited connective tissue disorders.
Family 5 - Saudi brothers homozygous for ATP6V1E1:c.634C>T, p.Arg212Trp (2 alleles reported in gnomAD v4.1.1., no hom). Seq method: WES followed by WGS (ATP6V1E1 variant missed by WES due to poor coverage).
The sibs presented with cutis laxa, dysmorphic facial features, strabismus, congenital heart defects, nephrocalcinosis, midline cleft palate. Pregnancy was complicated by oligohydramnios and hydronephrosis. Parents are first cousins, unaffected.

PMID: 28065471 Van Damme et al., 2018
Report of 5 families with syndromic cutis laxa and biallelic variants in ATP6V1E1 (2 families from Iran and Kuwait) and ATP6V1A (3 families from Germany, Turkey, and Pakistan).
Both families with ATP6V1E1 variants were consanguineous, and the probands were homozygous for a ATP6V1E1 variant each: c.383T>C, p.Leu128Pro in PI & c.634C>T, p.Arg212Trp in PII.
Variant p.Leu128Pro not found in gnomAD v4.1.1.
Patient phenotypes: cutis laxa 2/2, severe hypotonia 1 (1 not determined), cardiac abnormalities 2/2, aortic dilation 1/2, contractures 1/2; seizures and MRI abnormalities were not determined.
All parents reported to be unaffected.

This gene is associated with Cutis laxa, autosomal recessive, type IIC, OMIM:617402 in OMIM, and ATP6V1E1-related cutis laxa (biallelic_autosomal) in G2P with a Strong confidence level (resources accessed 9th Sept 2026).
Sources: Literature
Ehlers Danlos syndrome with a likely monogenic cause v4.17 ATP6V1A Ida Ertmanska changed review comment from: PMID: 33320377 Vogt et al., 2021
Report of three affected individuals with a severely progeroid form of congenital cutis laxa with generalized muscular hypotonia (2 sibs from a Hungarian family and a boy from a consanguineous Turkish family). Method: WES.

Male proband from Family A showed generalized cutis laxa with redundant skin and muscular hypotonia, progeroid appearance, bilateral leg weakness, bilateral contractures of his hips and knees; muscle biopsy revealed increased connective and fatty tissue, increased variability of fiber size, rounded fibers, some central nuclei and degenerating fibers with vacuoles. CK was strongly elevated. He died at 8 days of age due to cardiac and respiratory failure. His brother was similarly affected, but his symptoms improved and he is alive at 17 years old. Although weak muscle tone and thin skin remained, he has normal cognition and attends high school. Proband was comp het for ATP6V1A variants: c.317 T > C, p.(Leu106Ser) & c.1513_1514del, p.(Asp505*)

Male proband from Family B presented at birth with generalized muscular hypotonia, retrognathia and severe cutis laxa. He had normal speech and cognitive development. General muscular hypotonia and weakness were noted at age 4 years. Cranial MRI showed a cortical atrophy. His CK was elevated. His muscle weakness improved over time - he had normal endurance and muscle strength without any progression or loss of motor functions at 15yo. He was found to be homozygous for ATP6V1A: c.284 T > A, p.(Met95Lys).; to: BIALLELIC CASES:
PMID: 33320377 Vogt et al., 2021
Report of three affected individuals with a severely progeroid form of congenital cutis laxa with generalized muscular hypotonia (2 sibs from a Hungarian family and a boy from a consanguineous Turkish family). Method: WES. No seizures noted in either family.

Male proband from Family A showed generalized cutis laxa with redundant skin and muscular hypotonia, progeroid appearance, bilateral leg weakness, bilateral contractures of his hips and knees; muscle biopsy revealed increased connective and fatty tissue, increased variability of fiber size, rounded fibers, some central nuclei and degenerating fibers with vacuoles. CK was strongly elevated. He died at 8 days of age due to cardiac and respiratory failure. His brother was similarly affected, but his symptoms improved and he is alive at 17 years old. Although weak muscle tone and thin skin remained, he has normal cognition and attends high school. Proband was comp het for ATP6V1A variants: c.317 T > C, p.(Leu106Ser) & c.1513_1514del, p.(Asp505*)

Male proband from Family B presented at birth with generalized muscular hypotonia, retrognathia and severe cutis laxa. He had normal speech and cognitive development. General muscular hypotonia and weakness were noted at age 4 years. Cranial MRI showed a cortical atrophy. His CK was elevated. His muscle weakness improved over time - he had normal endurance and muscle strength without any progression or loss of motor functions at 15yo. He was found to be homozygous for ATP6V1A: c.284 T > A, p.(Met95Lys).

PMID: 28065471 Van Damme et al., 2017
Report of 5 families with syndromic cutis laxa and biallelic variants in ATP6V1E1 (2 families from Iran and Kuwait) and ATP6V1A (3 families from Germany, Turkey, and Pakistan). 2/3 families with ATP6V1A variants were consanguineous, and the probands were homozygous for the same ATP6V1A variant: c.215G>A, p.Gly72Asp. The German proband was homozygous for c.1012C>T, p.Arg338Cys.
Patient phenotypes: cutis laxa 3/3, severe hypotonia 3/3, cardiac abnormalities 3/3, aortic dilation 1/3, seizures 2/2 (1 not determined), contractures 1/3, MRI abnormalities (3/3 - 1 mild with an anatomical variant of the cavum septum pellucidum).
All parents reported to be unaffected.

MONOALLELIC CASES:
PMID: 40225911 Ma et al., 2024
Literature review of 31 previously reported cases with monoallelic de novo missense ATP6V1A variants and a Developmental and epileptic encephalopathy (DEE), plus two new cases with de novo heterozygous variants: c.1061G>T/p.(Trp354Leu) and c.746C>T/p.(Pro249Leu).
Common patient features from literature review: seizures (28/33), global developmental delay (29/33), hypotonia in infancy (24/33). Seizures mostly started within first 3 years of life (23/33). Most patients had no speech or poor language skills, which correlated with seizure severity. Brain MRI of 22 patients showed: hypomyelination in 13 patients, mild brain and cerebellar atrophy in 13 patients, thin corpus callosum in 4 patients, and bilateral lateral ventricle body broaden in one patient.

ATP6V1A is associated with Cutis laxa, autosomal recessive, type IID and AD Developmental and epileptic encephalopathy 93 in OMIM (Accessed 9th Sept 2026).