1. Panels
  2. Intellectual disability
  3. TMEM161B
Genes in panel
Prev Next
Regions in panel
Prev Next

Intellectual disability

Gene: TMEM161B

Amber List (moderate evidence)
TMEM161B (transmembrane protein 161B)
EnsemblGeneIds (GRCh38): ENSG00000164180
EnsemblGeneIds (GRCh37): ENSG00000164180
TMEM161B is in 5 panels

1 review

Ida Ertmanska (Genomics England Curator)

Green List (high evidence)

Comment on list classification: There are more than 3 unrelated probands reported in literature with biallelic TMEM161B variants and severe intellectual disability / developmental delay. Hence, this gene can be promoted to Green.
Created: 3 Nov 2026, 2:25 p.m. | Last Modified: 3 Nov 2026, 2:25 p.m.
Panel Version: 11.77
PMID: 36669109 Wang et al., 2023
Study of a polymicrogyria (PMG) cohort identified four families with affected children showing nearly identical neocortical PMG. Brain imaging in each showed dramatic symmetrical PMG, without a clear lobar or regional predominance. WES revealed homozygous variants in TMEM161B: c.949C>T; p.W317R in Families I & II, and c.254T>G; p.L85R in Families III and IV. All 4 families were from Egypt and had consanguinity reported; it is not known if probands with the same variants are related, so best to score as 2 independent families. Parents unaffected. Mild microcephaly reported at birth (HC -0.5 to -1.5 SD), progressing to severe at last examination in all 4 probands (head circumference -3 to -4.5 SD). Intellectual disability was moderate to profound. All individuals had seizures, with onset in the first few months of life. No cardiovascular abnormalities, no ophthalmic features apart from megalocornea in 1 family.

PMID: 37486637 Akula et al., 2023
Proband BFP903-905 - comp het for TMEM161B variants: c.362C>T p.Thr121Ile & c.580G>A p.Glu194Lys. Diffuse PMG, bilateral (neuropathologic examination) of BFP906, 903-905 similar clinical syndrome with no imaging. Head circumference unknown. Same variants as third family in PMID: 36669111 (same research group) - likely the same proband.

PMID: 36669111 Akula et al., 2023
Study describes 3 families with probands either homozygous or compound heterozygous for variants in TMEM161B. Variants described in the article are missense or splice site (splice site was shown in PMID 38593811 to result in skipping of exon 8).
Individual 09DG00538, Family A - presented at birth after normal delivery with intractable seizures, severe microcephaly, and hypotonia/spastic paresis; an MRI revealed diffuse PMG.
Individual UDN172478, Family B- diffuse PMG, pachygyria
4 sibs in Family C - presented with spastic hemiparesis, dysarthria, intellectual disability, and seizures. Diffuse PMG was discovered in the eldest sibling on autopsy; brain imaging unavailable for other sibs.

Article also generated and described TMEM161B null mice which broadly phenocopy the clinical indications described in the 3 families (null mice show holoprosencephaly, craniofacial midline defects, eye defects, and spinal cord patterning changes).

TMEM161B is not yet associated with a phenotype in OMIM (accessed 3rd Nov 2026).
Sources: Literature
Created: 3 Nov 2026, 2:08 p.m. | Last Modified: 3 Nov 2026, 2:21 p.m.
Panel Version: 11.76

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
polymicrogyria, MONDO:0000087; microcephaly, MONDO:0001149; epilepsy, MONDO:0005027

Publications

Created: 3 Nov 2026, 2:08 p.m.
Last Modified: 3 Nov 2026, 2:25 p.m.
Panel version: 11.76

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • Literature
Phenotypes
  • polymicrogyria, MONDO:0000087
  • microcephaly, MONDO:0001149
  • epilepsy, MONDO:0005027
Tags
Q4_26_promote_green
Clinvar variants
Variants in TMEM161B
Penetrance
None
Publications
Panels with this gene

History Filter Activity

3 Nov 2026, Gel status: 2

Entity classified by Genomics England curator

Ida Ertmanska (Genomics England Curator)

Gene: tmem161b has been classified as Amber List (Moderate Evidence).

3 Nov 2026, Gel status: 1

Created, Added New Source, Added Tag, Set mode of inheritance, Set publications, Set Phenotypes

Ida Ertmanska (Genomics England Curator)

gene: TMEM161B was added gene: TMEM161B was added to Intellectual disability. Sources: Literature Q4_26_promote_green tags were added to gene: TMEM161B. Mode of inheritance for gene: TMEM161B was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TMEM161B were set to 36669109; 36669111; 38593811; 37486637 Phenotypes for gene: TMEM161B were set to polymicrogyria, MONDO:0000087; microcephaly, MONDO:0001149; epilepsy, MONDO:0005027 Review for gene: TMEM161B was set to GREEN