Intellectual disability
Gene: C16orf62

C16orf62 (chromosome 16 open reading frame 62)
EnsemblGeneIds (GRCh38): ENSG00000103544
EnsemblGeneIds (GRCh37): ENSG00000103544
C16orf62 is in 9 panels

2 reviews

Ida Ertmanska (Genomics England Curator)

Green List (high evidence)

Comment on list classification: There are now 5 unrelated probands reported in literature with biallelic VPS35L (old name C16orf62) variants, and Ritscher-Schinzel syndrome. Both missense and nonsense variants have been reported. Of 5 probands, 4 were noted to have intellectual disability/ developmental delay, though explicitly described as profound in only one case, and mild in 2 others. Based on available evidence, this gene can be promoted to Green on Intellectual disabiity.
Created: 23 Oct 2026, 3:16 p.m. | Last Modified: 23 Oct 2026, 3:20 p.m.

Panel Version: 11.53

PMID: 42144185 Carelli et al., 2026
Case report of a North African male infant with Ritscher-Schinzel syndrome, harbouring a homozygous VPS35L variant (NM_020314.7: c.881T > C; p.(Phe294Ser)). Method: Trio WES. Proband presented with failure to thrive, with a weight of 2020 g (−2.9 SDS), length of 45 cm (−7.8 SDS), and head circumference of 31 cm (−7.5 SDS). He also had facial dysmorphism, severe axial hypotonia, limb anomalies including bilateral ulnar deviation of the fingers, splenomegaly, suspected unilateral cryptorchidism. Brain MRI showed multiple anomalies, particularly cerebellar and cortical dysplasia. No evident neurodevelopmental delay at 14 months. Trio exome detected a homozygous VPS35L variant NM_020314.7:c.881T > C; p.(Phe294Ser) in the proband, parents confirmed het.

PMID: 36113987 Otsuji et al., 2023
Reported 3 unrelated patients with biallelic VPS35L variants. Overlapping clinical features included GDD, ID (mild in 2 individuals and profound in 1), short stature (short stature between −2 and −3 SD in 2 probands, and -6 SD in one), brain anomalies on imaging, craniofacial dysmorphism, ophthalmological malformation (glaucoma in 2/3), skeletal complications (Brachymelia/Brachydactyly in 2 probands and reduced distal creases in 3), and cryptorchidism. 2 probands had biallelic nonsense variants, while the third proband, most severely affected, was homozygous for a missense variant VPS35L: p.P876L.

PMID: 31712251 Kato et al., 2020
Report of 2 Japanese sibs (boy & girl) with Ritscher-Schinzel syndrome and compound heterozygous pathogenic variants (c.1097dup; p.Cys366Trpfs*28 and c.2755G>A; p.Ala919Thr) in VPS35L. The individuals presented with cranio-cerebello-cardiac dysplasia, coloboma, microphthalmia, chondrodysplasia punctata and complicated skeletal malformation. The elder sister died at 28 days old. The male proband showed severe postnatal growth retardation at 3 yrs old. His length was 75cm (−6.2 SD), body weight was 8.2kg (−3.8 SD) and head circumference was 47cm (third percentile). His skeletal complication affected the whole body with vertebral body hypo-ossification, breast bone aplasia, shortened ulnae with radial bowing, short limbs and chondrodysplasia punctata with brachytelephalangy and first metacarpals and metatarsals shortening. He had GDD and ID.

VPS35L is associated with AR Ritscher-Schinzel syndrome 3, OMIM:619135 (OMIM accessed 23rd Oct 2026).
Created: 23 Oct 2026, 3:01 p.m. | Last Modified: 23 Oct 2026, 3:18 p.m.

Panel Version: 11.53

Comment on phenotypes: OMIM phenotype added 1st May 2026.
Created: 1 May 2026, 2:48 p.m. | Last Modified: 1 May 2026, 2:48 p.m.

Panel Version: 9.404

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Ritscher-Schinzel syndrome 3, OMIM:619135; Ritscher-Schinzel syndrome 3, MONDO:0030864

Publications

Created: 1 May 2026, 2:48 p.m.
Last Modified: 23 Oct 2026, 3:20 p.m.
Panel version: 11.53

Sarah Leigh (Genomics England Curator)

I don't know

Comment on list classification: Not associated with phenotype in OMIM or in Gen2Phen. Two variants have been reported as compound heterozygotes in two sibs with features of 3C/Ritscher-Schinzel syndrome. Functional studies show that loss of VPS35L function results in impared autophagy and VPS35L knockout mouse resulted in early embrionic lethality (PMID 31712251).
Created: 5 Jun 2020, 7:44 a.m. | Last Modified: 8 Jun 2020, 11:15 a.m.

Panel Version: 3.84

The HGNC approved name for this gene is: VPS35 endosomal protein sorting factor like (VPS35L)
Created: 5 Jun 2020, 7:29 a.m. | Last Modified: 5 Jun 2020, 7:29 a.m.

Panel Version: 3.81

Sources: Literature
Created: 5 Jun 2020, 7:20 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
3C/Ritscher-Schinzel-like syndrome

Publications

25434475

Created: 5 Jun 2020, 7:20 a.m.
Last Modified: 8 Jun 2020, 11:15 a.m.
Panel version: 3.81

Details

Mode of Inheritance

BIALLELIC, autosomal or pseudoautosomal

Sources

Expert Review Amber
Literature

Phenotypes

Ritscher-Schinzel syndrome 3, OMIM:619135
Ritscher-Schinzel syndrome 3, MONDO:0030864

Tags

new-gene-name gene-checked Q4_26_promote_green

Clinvar variants

Variants in C16orf62

Penetrance

None

Publications

Panels with this gene