ROGDI

Chr 16AR

rogdi atypical leucine zipper

Also known as: KTZS, RAV2, ROGD1

NCBI Gene: 79641 ENSG00000067836 UniProt: Q9GZN7 OMIM: 614574

The ROGDI protein is involved in brain development, neurogenesis, and tooth dentin formation, and is located in the nuclear envelope. Mutations cause Kohlschutter-Tonz syndrome, a rare autosomal recessive disorder characterized by early-onset seizures, intellectual disability, and distinctive dental abnormalities. The gene shows tolerance to loss-of-function variants (very low pLI score), which is consistent with the recessive inheritance pattern observed clinically.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM

Involved in brain development; neurogenesis; and odontogenesis of dentin-containing tooth. Located in nuclear envelope. Implicated in Kohlschutter-Tonz syndrome. [provided by Alliance of Genome Resources, Jul 2025]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Kohlschutter-Tonz syndromeMIM #226750

UniProtKohlschuetter-Toenz syndrome

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · amelocerebrohypohidrotic syndrome · AR · ClinGen 2022

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.42

LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — ROGDI

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.42LOEUF

pLI 0.000

Z-score 0.32

OE 0.91 (0.60–1.42)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-1.32Z-score

OE missense 1.29 (1.15–1.45)

212 obs / 164.3 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.91 (0.60–1.42)

0≤0.351.4

Missense OE?1.29 (1.15–1.45)

0≤0.61.4

Synonymous OE?1.66

0≤1.21.6

LoF obs/exp: 14 / 15.4Missense obs/exp: 212 / 164.3Syn Z: -4.35

Background carrier burden — how many people carry a rare variant somewhere in ROGDI?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

626 rare PASS variants

Rare truncating (LoF)

1 in 510

104 rare PASS variants

Rare synonymous (reference)

1 in 140

221 rare PASS variants

Rare missense and truncating variants are carried at similar rates in ROGDI; this gene does not show strong loss-of-function constraint by this measure. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 150	1 in 1,600
South Asian	~43k	1 in 120	1 in 1,300
Remaining (unassigned)	~30k	1 in 65	1 in 1,900
European (Finnish)	~27k	1 in 340	1 in 2,500
Admixed American	~22k	1 in 81	1 in 820
African / African American	~21k	1 in 68	1 in 1,000
East Asian	~20k	1 in 80	1 in 4,000
Ashkenazi Jewish	~13k	1 in 240	≈ 1 in 3,300
Middle Eastern	~2,884	1 in 100	≈ 1 in 960

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.